Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 631
Filter
1.
Braz. j. biol ; 83: e246040, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1285610

ABSTRACT

Abstract Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by a congenitally reduced head circumference (-3 to -5 SD) and non-progressive intellectual disability. The objective of the study was to evaluate pathogenic mutations in the ASPM gene to understand etiology and molecular mechanism of primary microcephaly. Blood samples were collected from various families across different remote areas of Pakistan from February 2017 to May 2019 who were identified to be affected with primary microcephaly. DNA extraction was performed using the salting-out method; the quality and quantity of DNA were evaluated using spectrophotometry and 1% agarose gel electrophoresis, respectively in University of the Punjab. Mutation analysis was performed by whole exome sequencing from the Cologne Center for Genomics, University of Cologne. Sanger sequencing was done in University of the Punjab to confirm the pathogenic nature of mutation. A novel 4-bp deletion mutation c.3877_3880delGAGA was detected in exon 17 of the ASPM gene in two primary microcephaly affected families (A and B), which resulted in a frame shift mutation in the gene followed by truncated protein synthesis (p.Glu1293Lysfs*10), as well as the loss of the calmodulin-binding IQ domain and the Armadillo-like domain in the ASPM protein. Using the in-silico tools Mutation Taster, PROVEAN, and PolyPhen, the pathogenic effect of this novel mutation was tested; it was predicted to be "disease causing," with high pathogenicity scores. One previously reported mutation in exon 24 (c.9730C>T) of the ASPM gene resulting in protein truncation (p.Arg3244*) was also observed in family C. Mutations in the ASPM gene are the most common cause of MCPH in most cases. Therefore, enrolling additional affected families from remote areas of Pakistan would help in identifying or mapping novel mutations in the ASPM gene of primary microcephaly.


Resumo Microcefalia primária autossômica recessiva (MCPH) é um distúrbio do neurodesenvolvimento caracterizado por uma redução congênita do perímetro cefálico (-3 a -5 DP) e deficiência intelectual não progressiva. O objetivo do estudo foi avaliar mutações patogênicas no gene ASPM a fim de compreender a etiologia e o mecanismo molecular da microcefalia primária. Amostras de sangue foram coletadas de várias famílias em diferentes áreas remotas do Paquistão de fevereiro de 2017 a maio de 2019, que foram identificadas como afetadas com microcefalia primária. A extração do DNA foi realizada pelo método salting-out; a qualidade e a quantidade de DNA foram avaliadas por espectrofotometria e eletroforese em gel de agarose a 1%, respectivamente, na Universidade de Punjab. A análise de mutação foi realizada por sequenciamento completo do exoma do Cologne Center for Genomics, University of Cologne. O sequenciamento de Sanger foi feito na Universidade do Punjab para confirmar a natureza patogênica da mutação. Uma nova mutação de deleção de 4 bp c.3877_3880delGAGA foi detectada no exon 17 do gene ASPM em duas famílias afetadas por microcefalia primária (A e B), que resultou em uma mutação de frame shift no gene seguida por síntese de proteína truncada (pGlu1293Lysfs * 10), bem como a perda do domínio IQ de ligação à calmodulina e o domínio do tipo Armadillo na proteína ASPM. Usando as ferramentas in-silico Mutation Taster, PROVEAN e PolyPhen, o efeito patogênico dessa nova mutação foi testado; foi previsto ser "causador de doenças", com altos escores de patogenicidade. Uma mutação relatada anteriormente no exon 24 (c.9730C > T) do gene ASPM, resultando em truncamento de proteína (p.Arg3244 *) também foi observada na família C. Mutações no gene ASPM são a causa mais comum de MCPH na maioria dos casos . Portanto, a inscrição de famílias afetadas adicionais de áreas remotas do Paquistão ajudaria a identificar ou mapear novas mutações no gene ASPM da microcefalia primária.


Subject(s)
Humans , Microcephaly/genetics , Nerve Tissue Proteins/genetics , Pakistan , Consanguinity , Mutation/genetics
2.
Gerais (Univ. Fed. Juiz Fora) ; 14(2): 1-23, maio-ago. 2021.
Article in Portuguese | LILACS, INDEXPSI | ID: biblio-1286607

ABSTRACT

Este estudo buscou investigar as concepções de família de psicólogos dos Centros de Referência de Assistência Social (CRAS). Para isso, foram realizadas entrevistas individuais com cinco psicólogos inseridos nos CRAS de uma cidade do Rio Grande do Sul, a fim de acessar suas crenças, valores e representações envolvendo o conceito de família. A partir da análise qualitativa de conteúdo, os resultados indicaram que os participantes consideraram família as pessoas que estabelecem relações a partir de laços afetivos, não restringindo sua definição à consanguinidade. Ainda, apontaram como indicadores de saúde familiar a capacidade de cuidar dos filhos, manejar conflitos e a não violência. Todavia, alguns participantes apresentaram resquícios de uma visão de família tradicional e romantizada. Ressalta-se a importância de a atuação do psicólogo estar atrelada à capacidade de analisar criticamente o contexto de atuação e a realidade social brasileira. A partir disso, espera-se contribuir para a construção de uma prática que não reproduza a violência social e a estigmatização das famílias atendidas.


This study sought to investigate the family conceptions of psychologists at the Social Assistance Reference Centers (CRAS). For this, individual interviews were conducted with five psychologists inserted in the CRAS of a city of Rio Grande do Sul, in order to access their beliefs, values ​​and representations involving the concept of family. From the qualitative analysis of content, the results indicated that the participants considered family the persons who establish relationships based on emotional ties, not restricting their definition to consanguinity. In addition, they pointed out as indicators of family health the ability to take care for children, handle conflicts and non-violence. However, some participants presented traces of a traditional and romanticized family view. The importance of the psychologist's performance is linked to the ability to critically analyze the context of practice and the Brazilian social reality. From this, it is expected to contribute to the construction of a practice that does not reproduce social violence and stigmatization of the families served.


Subject(s)
Social Support , Family , Psychology , Social Work , Health Centers , Consanguinity
3.
Med. lab ; 25(1): 409-418, 2021. tab, maps
Article in Spanish | LILACS | ID: biblio-1292646

ABSTRACT

El papel de la endogamia como causa de homocigosidad en la salud humana es un foco de interés en genética médica, debido a su relación con anomalías congénitas y patologías genéticas recesivas. Es un tema importante a pesar de que las tasas de uniones consanguíneas en ciertas sociedades han disminuido con el tiempo; sin embargo, en algunas comunidades se han mantenido estables o han aumentado. La consanguinidad es practicada hasta en el 10% de la población mundial, y los motivos más comúnmente citados son socioculturales y socioeconómicos. Aunque se ha visto una disminución de esta práctica, probablemente por la migración urbana y el aumento de las tasas de educación, la consanguinidad continúa practicándose en todo el mundo. Los efectos más significativos sobre los resultados reproductivos se deben, principalmente, a condiciones hereditarias autosómicas recesivas, que también aumentan la frecuencia de algunos desórdenes médicos. El objetivo de esta revisión es dar a conocer la epidemiología y los factores predisponentes de la consanguinidad, así como presentar la evidencia actual de la asociación entre la consanguinidad originada en la endogamia y las anormalidades congénitas y patologías médicas como consecuencia de trastornos genéticos mendelianos. Se requiere un enfoque culturalmente apropiado para el asesoramiento genético en relación con la endogamia


The role of consanguinity as a cause of homozygosity in human health is a focus of interest in medical genetics, due to its relationship with congenital anomalies and recessive genetic pathologies. This is an important issue since the rates of consanguineous unions in certain societies have decreased over time, but have remained stable or have increased in others. Consanguinity is practiced in up to 10% of the world population, and the most common reasons are sociocultural and socioeconomic factors. Although there has been a decrease in this practice, probably due to urban migration and an increase in education rates, consanguinity continues to be practiced throughout the world. The most significant effects on reproductive outcomes are mainly due to autosomal recessive hereditary conditions, that also increase the frequency of medical disorders. The aim of this review is to present the current evidence of the association between consanguinity originating from endogamy, with congenital abnormalities and medical disorders originated from mendelian genetic pathologies. A cultural appropriate approach is required for genetic counseling in relation to consanguineous endogamy


Subject(s)
Humans , Consanguinity , Congenital Abnormalities , Founder Effect , Inbreeding
4.
Article in Chinese | WPRIM | ID: wpr-921949

ABSTRACT

OBJECTIVE@#To analyze gene variants in a Chinese pedigree with oculocutaneous albinism (OCA).@*METHODS@#Gene sequencing of the proband and his parents was performed using chip capture high-throughput sequencing and Sanger sequencing techniques, and PolyPhen-2, SIFT, MutationTaster, and FATHMM software were used to predict the function of new variants. At the same time,the pedigree and variant genes of 4 albinism patients from this pedigree were analyzed.@*RESULTS@#Sequencing results showed that the proband's TYR gene (NM_000372) has c.230G>A (p.Arg77Gln) and c.120_121insG (p.Asp42GlyfsTer35) compound heterozygous variants. The proband's father carries c.230G>A heterozygous variant, and the mother carries c.120_121insG heterozygous variant, indicating that the proband's two variants are from his father and mother. The former is a known missense variant, which can cause abnormal or loss of the original function of the protein polypeptide chain. The latter c.120_121insG(p.Asp42GlyfsTer35) is an unreported frameshift variant of the TYR gene subregion (EX1; CDS1). PolyPhen-2, SIFT, MutationTaster and FATHMM predictions are all prompted as "harmful variants". This variant caused the amino acid encoded protein to terminate prematurely, producing a truncated protein, which eventually formed a 76-amino acid short-type TYR protein instead of the 529-amino acid wild-type TYR protein. Through the pedigree analysis, the four patients in the pedigree are all of the same type of compound heterozygous variants, and the disease-causing genes are all from the patient's parents. They belong to a special form of consanguineous marriage within 5 generations.@*CONCLUSION@#The compound heterozygous variants of c.230G>A (p.Arg77Gln) and c.120_121insG (p.Asp42GlyfsTer35) of the TYR gene may underlie the disease in this pedigree. The gene sequencing results enrich the variant spectrum of the TYR gene, and has facilitated molecular diagnosis for the patient.


Subject(s)
Albinism, Oculocutaneous/genetics , Consanguinity , Heterozygote , Humans , Mutation , Pedigree
5.
Article in Chinese | WPRIM | ID: wpr-826546

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a consanguineous pedigree affected with inherited coagulation factor V deficiency.@*METHODS@#Genomic DNA was extracted from peripheral blood samples from the pedigree and subjected to next generation sequencing for screening variants of the F5 gene. Suspected pathogenic variant was verified by using Sanger sequencing. Pathogenicity of the variant was evaluated according to ACMG guidelines.@*RESULTS@#A homozygous frameshifting variant, c.4096delC (p.Leu1366Phefs*3), was identified in the F5 gene in the proband, which was confirmed to be derived from her consanguineous parents. This variant was absent in all databases including 10 000 in-house Chinese exome sequences. Based on the ACMG guidelines, the c.4096delC was predicted to be a pathogenic variant.@*CONCLUSION@#A novel pathogenic variant has been identified in the F5 gene in a consanguineous pedigree with inherited coagulation factor V deficiency, which has enriched the spectrum of F5 gene variants.


Subject(s)
Consanguinity , Factor V , Genetics , Factor V Deficiency , Genetics , Female , Genetic Variation , Humans , Pedigree
6.
Rev. cuba. med. gen. integr ; 35(2): e842, abr.-jun. 2019. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1093488

ABSTRACT

Introducción: La consanguinidad continúa siendo un fenómeno universal, hoy día los matrimonios consanguíneos y su descendencia suponen aproximadamente el 10,4 por ciento de la población mundial; sus descendientes tienen una elevada probabilidad de padecer enfermedades mendelianas recesivas, así como enfermedades complejas de naturaleza multifactorial. Objetivos: Determinar el coeficiente de endogamia de la región y las principales afectaciones encontradas en la descendencia de matrimonios consanguíneos. Métodos: Se realizó una investigación descriptiva, aplicada y retrospectiva de corte transversal sobre coeficiente de endogamia en el Consejo Popular Paso Quemado, municipio Los Palacios, Pinar del Río, en el período comprendido entre mayo 2016 y febrero 2017. Resultados: Fueron identificados 11 matrimonios consanguíneos (1,96 por ciento), mayormente en área rural y entre primos hermanos. El coeficiente de endogamia medio fue 0,00115. Después de la década del 70 no se efectuaron matrimonios consanguíneos. Afectaciones como mortalidad infantil, enfermedades monogénicas raras, malformaciones congénitas, discapacidad intelectual leve y enfermedades comunes aparecieron con mayor frecuencia en la descendencia de primos hermanos. Conclusiones: En correspondencia con la apertura de nuevas oportunidades sociales, económicas y educativas en la región la consanguinidad no constituye hoy en día un problema de salud, no obstante 52,5 por ciento de la descendencia en consanguíneos resultó afectada, mayormente por enfermedades complejas. El estudio sienta las bases para establecer una estrategia de educación y promoción de salud a nivel comunitario(AU)


Introduction: Consanguinity continues to be a universal phenomenon. Nowadays, consanguineous marriages and their descendants are estimated at 10,4 percent of the world population; their descendants have a high probability of suffering recessive Mendelian diseases, as well as complex diseases of multifactorial nature. Objectives: To determine the inbreeding coefficient of the region and the main affectations found in offspring of consanguineous marriages. Methods: A descriptive, applied and retrospective cross-sectional research on the inbreeding coefficient was conducted at Paso Quemado Popular Council, Los Palacios Municipality, Pinar del Río, from May 2016 to February 2017. Results: We identified 11 consanguineous marriages (1.96 percent), mostly in rural areas and among first cousins. The average inbreeding coefficient was 0.00115. After the 70's, there was no occurrence of consanguineous marriages. Affectations such as infant mortality, rare monogenic diseases, congenital malformations, mild intellectual disability and common diseases appeared more frequently in the offspring of first cousins. Conclusions: In correspondence with the opening of new social, economic and educational opportunities in the region, consanguinity does not constitute a health problem nowadays; however, mostly complex diseases affected 52.5 percent of offspring in consanguineous couples. The study lays the foundations to establish a health education and promotion strategy at the community level(AU)


Subject(s)
Humans , Male , Female , Consanguinity , Health Promotion , Epidemiology, Descriptive , Cross-Sectional Studies , Retrospective Studies
7.
Rev. cuba. pediatr ; 91(1): e441, ene.-mar. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-985592

ABSTRACT

Introducción: Existen pocas investigaciones sobre factores de riesgo de tumores renales pediátricos. Objetivo: Caracterizar en detalle regiones geográficas de alta incidencia de tumores renales pediátricos en el centro de Argentina y su posible vinculación con factores de riesgo genéticos. Métodos: El área de estudio comprendió la provincia de Córdoba (Argentina). Se generó una base de datos de incidencia del cáncer renal infantil con información del Registro Provincial de Tumores. Se realizaron análisis de conglomerados espaciotemporales. En localidades dentro de los conglomerados, se llevaron a cabo entrevistas en profundidad a informantes claves. Resultados: Se registraron 56 casos de tumores renales pediátricos en el Registro en el periodo 2004-2013. Se detectó un conglomerado espacial significativo que abarca siete departamentos de la provincia. En esa región se concretaron seis entrevistas en profundidad a informantes claves. Los entrevistados resaltaron la mayor frecuencia de enfermedad genética de Sandhoff y las prácticas de endogamia (corroboradas en numerosos resultados científicos). A partir de estos datos se determinaron zonas de superposición de tumores renales y de la enfermedad de Sandhoff. Conclusiones: Se detectó una región particular de la provincia con alta frecuencia de tumores renales pediátricos y de la enfermedad de Sandhoff. Numerosos estudios científicos determinan que la endogamia es el factor de riesgo que aumenta la frecuencia de esta enfermedad en esta región. En futuras investigaciones se deberá corroborar si la endogamia también actúa aumentando la incidencia de tumores renales infantiles(AU)


Introduction: There is little research on risk factors of pediatric renal tumors. Objective: To characterize in detail the geographic regions of greatest incidence of pediatric renal tumors in central Argentina and exploring their possible link to genetic risk factors. Methods: The study area comprised the province of Córdoba (Argentina), and a database of pediatric renal tumors incidence was generated with information from the Provincial Tumor Registry. Analyses of spatio-temporal clusters were performed. In-depth interviews with key informants were carried out at localities within the conglomerates. Results: 56 cases of pediatric renal tumors were registered in the Provincial Registry of Tumors between 2004 and 2013. A significant spatial conglomerate was detected, covering seven districts of the province. In that region, six in-depth interviews were conducted with key informants. Interviewees highlighted the increased frequency of Sandhoff genetic disease and endogamous practices (corroborated in numerous scientific results). From these data, zones of overlap of renal tumors and of Sandhoff disease were determined. Conclusions: A particular region of the province was detected with high frequency of pediatric renal tumors and Sandhoff disease. Numerous scientific studies have determined that endogamy is the risk factor that increases the frequency of Sandhoff disease in this region. In future research, it should be confirmed whether it also acts by increasing the incidence of renal tumors in children(AU)


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Consanguinity , Genetic Predisposition to Disease/etiology , Kidney Neoplasms/complications , Kidney Neoplasms/epidemiology , Argentina , Space-Time Clustering , Kidney Neoplasms/genetics
8.
Pesqui. bras. odontopediatria clín. integr ; 19(1): 4401, 01 Fevereiro 2019. map, tab, graf
Article in English | LILACS, BBO | ID: biblio-998036

ABSTRACT

Objective: To determine the coefficient of inbreeding of consanguinity (F) and its correlates in Aligarh city, India. Material and Methods: Cross sectional household survey with a sample size of 2000 (1600 non-consanguineous and 400 consanguineous couples) using systematic random sampling. Researcher conducted the study by visiting every tenth household of every tenth ward of Aligarh city. Information was recorded on a pre-tested questionnaire, which had questions pertaining to religion, details regarding relationship between couples (consanguineous / non consanguineous marriage), type of consanguinity (first cousin/second cousin/third cousin), level of education and occupation (a proxy for socioeconomic status). Descriptive statistics, Chi-square, and multivariate logistic regression were used. Results: Multivariate logistic regression analysis showed that Islam (p<0.001) and Christianity (p<0.001) were significantly associated with consanguinity. Private employment with (-) B value (p<0.001) showed a significant association of the variable with non-consanguineous group. Coefficient of inbreeding for the present study was 0.0538, highest reported from any part of India. Conclusion: Consanguinity is a prevailing problem in Aligarh city, India. Evidence based guidelines needed. Information ­ education ­ communication and pre-marital counseling suggested to make population aware of the consequences of consanguinity and to help couples make a decision.


Subject(s)
Humans , Male , Female , Marriage , Cross-Sectional Studies/methods , Christianity/history , Consanguinity , Islam , Chi-Square Distribution , Prevalence , Multivariate Analysis , Surveys and Questionnaires
9.
Article in Chinese | WPRIM | ID: wpr-776768

ABSTRACT

OBJECTIVE@#To explore the genetic basis of a patient with early-onset Parkinson disease from a consanguineous family.@*METHODS@#Homozygosity mapping and Sanger sequencing of cDNA were used to identify the causative mutation.@*RESULTS@#A homozygous missense variation (c.56C>G, p.Thr19Arg) in the PARK7 gene was identified in the patient. In silico analysis suggested the c.56C>G variation to be pathogenic.@*CONCLUSION@#Homozygous c.56C>G variation of the PARK7 gene was the disease-causing variation in this family.


Subject(s)
Consanguinity , Homozygote , Humans , Mutation, Missense , Parkinson Disease , Genetics , Pedigree , Protein Deglycase DJ-1 , Genetics
10.
Arq. bras. oftalmol ; 81(5): 440-442, Sept.-Oct. 2018. graf
Article in English | LILACS | ID: biblio-950495

ABSTRACT

ABSTRACT We report on a case of two sisters, daughters of consanguineous parents, presenting with a similar condition of low visual acuity associated with retinal dystrophy in both eyes associated with alopecia and bone alterations or syndactyly.


RESUMO Relatamos um caso de duas irmãs, filhas de pais consanguíneos, apresentando uma condição semelhante de baixa acuidade visual associado à distrofia retiniana em ambos os olhos associado à alopecia e alterações ósseas ou sindactilia.


Subject(s)
Humans , Female , Child , Adolescent , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia/diagnostic imaging , Hand Deformities, Congenital/genetics , Hand Deformities, Congenital/diagnostic imaging , Consanguinity , Macular Degeneration/congenital , Siblings , Macular Degeneration/genetics , Macular Degeneration/diagnostic imaging
11.
EMHJ-Eastern Mediterranean Health Journal. 2018; 24 (7): 631-636
in English | IMEMR | ID: emr-199146

ABSTRACT

Background: Red reflex screening is the primary but unheeded test for the detection of vision- and life-threatening eye conditions.


Aims: To evaluate the red reflex of newborns, percentage of ocular diseases resulting in red reflex abnormality, and their relation with consanguinity in Southeast Turkey.


Methods: Newborns [n = 1358] were examined with pencil light and direct ophthalmoscopy.


Results: Eight hundred of these newborns were hospitalized in a rooming-in unit. [RIU] and 558 were in the neonatal intensive care service [NICS]. In the RIU there were 7 [0.88%] newborns with abnormal red reflex and in the NICS there were 14 [2.51%]. Sensitivity of pencil light examination was 71.4%. Studies from the Middle East have shown potential recessive genetic causes of common paediatric ocular conditions. In our study, consanguineous marriage was found to have a significant association with red reflex abnormality [P = 0.017].


Conclusions: Red reflex screening test is important in the early diagnosis of vision- and life-threatening eye disorders in Southeast Turkey where consanguinity is common


Subject(s)
Humans , Infant, Newborn , Consanguinity , Intensive Care, Neonatal , Infant, Newborn , Prospective Studies , Cataract/congenital , Hospitalization
12.
Braz. oral res. (Online) ; 32: e24, 2018. tab
Article in English | LILACS | ID: biblio-889479

ABSTRACT

Abstract: Considering that environmental risk factors substantially contribute to the etiology of orofacial clefts and that knowledge about the characteristics and comorbidities associated with oral clefts is fundamental to promoting better quality of life, this study aimed to describe the risk factors, main characteristics, and comorbidities of a group of patients with cleft lip and/or cleft palate (CL/P) from Rio Grande do Norte (RN), Brazil. Data were obtained from 173 patients with CL/P using a form from the Brazilian database on Orofacial Clefts. Most patients were male with cleft lip and palate and had a normal size and weight at birth; presented few neonatal intercurrent events; and had anemia and respiratory and cardiovascular diseases as main associated comorbidities. They also required timely surgical rehabilitation and multidisciplinary care to stimulate their neuropsychomotor development. In addition, a high frequency of familial recurrence and of parental consanguinity was evidenced in the studied population, especially for the cleft lip and cleft palate type. Other relevant findings were the considerable maternal exposure to alcohol, infections, smoking, and hypertension, as well as low supplementation with vitamins and minerals and deliberate consumption of analgesics, antibiotics, and antihypertensives during pregnancy. Characterization of the CL/P patient profile is essential for the planning of health services and integration among the health professionals involved in the diagnosis and treatment of these malformations. Our results reinforce the need for additional research to confirm the association between environmental factors and the development of orofacial clefts.


Subject(s)
Humans , Male , Female , Pregnancy , Infant , Child, Preschool , Child , Adolescent , Adult , Young Adult , Cleft Lip/epidemiology , Cleft Lip/etiology , Cleft Palate/epidemiology , Cleft Palate/etiology , Brazil/epidemiology , Cleft Lip/surgery , Cleft Palate/surgery , Comorbidity , Consanguinity , Maternal Age , Maternal Exposure , Prevalence , Risk Assessment , Risk Factors , Sex Factors , Smoking/adverse effects
13.
Arch. endocrinol. metab. (Online) ; 61(6): 633-636, Dec. 2017. graf
Article in English | LILACS | ID: biblio-887602

ABSTRACT

SUMMARY Isolated growth hormone deficiency (IGHD) is the most common pituitary hormone deficiency and, clinically, patients have delayed bone age. High sequence similarity between CYP21A2 gene and CYP21A1P pseudogene poses difficulties for exome sequencing interpretation. A 7.5 year-old boy born to second-degree cousins presented with severe short stature (height SDS −3.7) and bone age of 6 years. Clonidine and combined pituitary stimulation tests revealed GH deficiency. Pituitary MRI was normal. The patient was successfully treated with rGH. Surprisingly, at 10.8 years, his bone age had advanced to 13 years, but physical exam, LH and testosterone levels remained prepubertal. An ACTH stimulation test disclosed a non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency explaining the bone age advancement and, therefore, treatment with cortisone acetate was added. The genetic diagnosis of a homozygous mutation in GHRHR (p.Leu144His), a homozygous CYP21A2 mutation (p.Val282Leu) and CYP21A1P pseudogene duplication was established by Sanger sequencing, MLPA and whole-exome sequencing. We report the unusual clinical presentation of a patient born to consanguineous parents with two recessive endocrine diseases: non-classic congenital adrenal hyperplasia modifying the classical GH deficiency phenotype. We used a method of paired read mapping aided by neighbouring mis-matches to overcome the challenges of exome-sequencing in the presence of a pseudogene.


Subject(s)
Humans , Male , Infant , Child , Bone Diseases, Developmental/genetics , Steroid 21-Hydroxylase/genetics , Receptors, Neuropeptide/genetics , Adrenal Hyperplasia, Congenital/genetics , Dwarfism, Pituitary/genetics , Pedigree , Phenotype , Bone Diseases, Developmental/etiology , Receptors, Pituitary Hormone-Regulating Hormone/genetics , Adrenal Hyperplasia, Congenital/complications , Consanguinity , Dwarfism, Pituitary/complications , Mutation
14.
Ciênc. Saúde Colet ; 22(11): 3773-3780, Nov. 2017. tab
Article in Portuguese | LILACS | ID: biblio-890200

ABSTRACT

Resumo As hemoglobinas variantes (Hb) decorrem de mutações nos genes da globina. As variantes estruturais mais frequentes são HbS, HbC, HbD e HbE. O gene da hemoglobina S tem frequência elevada na América, enquanto que no Brasil é maior no Sudeste e Nordeste. O presente artigo tem por objetivo investigar a presença de hemoglobinas variantes em 15 comunidades quilombolas do estado do Piauí. Foram analisadas 1.239 amostras, nas quais as hemoglobinas foram triadas pela cromatografia líquida de alta eficiência (HPLC). Aplicou-se questionário referente a gênero, etnia e consanguinidade das populações. Das 1.239 amostras, 5,4% apresentaram o traço falciforme AS, as doenças falciformes SS e SC apareceram em 0,8% do total, nas hemoglobinas AC, AD e DD. Das 1.069 pessoas negras, 84 apresentaram alteração das hemoglobinas; destas, 34 eram do sexo masculino e 53 do feminino. Ocorreu a presença de 13 casamentos consanguíneos dentre as 84 alterações das hemoglobinas. O estudo das hemoglobinas variantes em 15 comunidades remanescentes de quilombos do Piauí contribui para sua educação em saúde frente aos aspectos da herança genética destas proteínas, relevante questão de saúde pública, proporcionando subsídios para a implantação do Programa Estadual da Doença Falciforme do Piauí.


Abstract Hemoglobin variants (Hb) result from mutations in globin genes, with amino acid substitution in the polypeptide chain. Among the most common structural variants are HbS, HbC, HbD and HbE. The S hemoglobin gene is a high frequency gene across America and Brazil, where it is more frequent in the Southeast and Northeast. The scope of this article is to investigate the presence of hemoglobin variants in 15 quilombos (fugitive slave communities) of Piaui. The sample was of 1,239 people and hemoglobin was screened by high-performance liquid chromatography (HPLC). A questionnaire was applied related to gender, ethnicity and consanguinity. Of the samples analyzed, 5.4% had AS sickle cell trait, while SS and SC sickle cell anemia showed a rate of 0.8%, with AC, AD and DD hemoglobin. Of the 1,069 Afro-descendants, 84 revealed hemoglobin abnormalities, 34 being male 53 being female. There were 13 consanguineous marriages among the 84 hemoglobin alterations. The study of hemoglobin variants in 15 former quilombo communities in the state of Piaui contributes to their education in health in the aspects of genetic inheritance of hemoglobin, a relevant public health issue, providing input for the implementation of the State Program of Sickle Cell Disease of Piaui.


Subject(s)
Humans , Male , Female , Sickle Cell Trait/epidemiology , Hemoglobins/genetics , Ethnicity/genetics , Anemia, Sickle Cell/epidemiology , Sickle Cell Trait/genetics , Genetic Variation , Brazil/epidemiology , Prevalence , Surveys and Questionnaires , Chromatography, High Pressure Liquid/methods , Consanguinity , Amino Acid Substitution/genetics , Blacks/genetics , Gene Frequency , Anemia, Sickle Cell/genetics
16.
Rev. colomb. psiquiatr ; 46(2): 82-87, Apr.-June 2017. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-960119

ABSTRACT

Abstract Introduction: Mental illness has been associated with violent behaviour. Criminal behaviour in the mentally ill population in Colombia has not been well studied. Methods: This is a retrospective, descriptive study, from a secondary source. An analysis was made of the sociodemographic, clinical, and legal variables of 127 unfit to plead patients. A descriptive analysis of quantitative variables was performed by measures of central tendency, and frequencies and percentages were calculated for the qualitative variables. The software SPSS® version 21.0 was used to analyse the data, and the study was approved by the Research Committee of the CES University. Results: The median age was 34 years, interquartile range 19 years, and 92.1% were men. The primary diagnosis was schizophrenia in 63%, 66.9% consumed alcohol, and 58.3% other drugs at the time they committed the crime. Almost one/third (29.1%) had a criminal record, and the most common type of crime was murder in 44.1% of cases. Around half (50.3%) of the victims had some degree of consanguinity with the patient. Discussion: The study subjects had higher illiteracy and lower educational levels than the Colombian prison population. Schizophrenia was the main diagnosis, and homicide the most prevalent crime, which agrees with the literature where non-indictable patients are responsible for 5-20% of murder cases worldwide. Conclusions: To reduce the gap between the diagnosis and treatment of mental disorders, especially schizophrenia, should be within the specific actions to prevent violence and criminal behaviour associated with mental illness.


Resumen Introducción: La enfermedad mental se ha asociado con comportamientos violentos. En Colombia poco se ha estudiado la población de enfermos mentales con comportamiento criminal. Métodos: Estudio descriptivo retrospectivo a partir de fuente secundaria. Se analizaron variables sociodemográficas, clínicas y legales de 127 pacientes inimputables. Se realizó análisis descriptivo de las variables cuantitativas a través de medidas de tendencia central, y para las variables cualitativas se obtuvieron frecuencias y porcentajes. La información se analizó con el software SPSS versión 21.0. La investigación fue aprobada por el Comité de Investigación de la Universidad CES. Resultados: La mediana de edad fue 34 [intervalo intercuartílico, 19] años; el 92,1% eran varones. El diagnóstico principal fue esquizofrenia en el 63%. En el momento de cometer el crimen, el 66,9% consumía alcohol y el 58,3%, drogas. El 29,1% tenía antecedentes delictivos y el tipo de delito más frecuente (44,1%) fue el homicidio. El 50,3% de las víctimas tenían algún grado de consanguinidad con el paciente. Discusión: En los sujetos del estudio había más analfabetismo y menor nivel educativo que en la población general carcelaria colombiana. La esquizofrenia fue el principal diagnóstico y el homicidio, el delito más prevalente, lo cual coincide con la literatura que refleja que los inimputables son responsables de un 5-20% de los casos de homicidio en el mundo. Conclusiones: Disminuir la brecha para el diagnóstico y el tratamiento de los trastornos mentales, especialmente la esquizofrenia, estaría entre las acciones concretas para prevenir la violencia y la conducta criminal asociada a enfermedad mental.


Subject(s)
Humans , Male , Adult , Schizophrenia , Criminal Behavior , Mental Disorders , Research , Violence , Software , Colombia , Consanguinity , Mentally Ill Persons , Literacy , Homicide
17.
Oman Medical Journal. 2017; 32 (1): 66-68
in English | IMEMR | ID: emr-185728

ABSTRACT

Mutations in the C19 or f12 gene are known to cause mitochondrial membrane protein associated neurodegeneration [MPAN], which is a neurodegeneration with brain iron accumulation [NBIA] type 4 disorder. To the best of our knowledge, this is the first report of a genetically confirmed case of MPAN from Oman. A novel homozygous deletion of exon 2 of the C19 or f12 gene was confirmed on the proband, a seven-year old girl, who presented with gait instability. Brain magnetic resonance imaging showed iron deposition on the basal ganglia. This report highlights the importance of genetic testing of such a clinically and genetically heterogeneous condition among a population with a high consanguinity rate. To overcome the diagnostic difficulty, implementation of a cost-effective approach to perform cascade screening of carriers at risk is needed as well as programs to address risky consanguineous marriages


Subject(s)
Child , Female , Humans , Brain/pathology , Mitochondrial Proteins/genetics , Consanguinity , Sequence Deletion
18.
IBJ-Iranian Biomedical Journal. 2017; 21 (5): 338-341
in English | IMEMR | ID: emr-188491

ABSTRACT

Background: Osteogenesis imperfecta [Ol] is a clinically and genetically heterogeneous disorder characterized by bone loss and bone fragility. The aim of this study was to investigate the variants of three genes involved in the pathogenesis of Ol


Methods: Molecular genetic analyses were performed for COLlAl, COL1A2, and CRTAP genes in an Iranian family with Ol. The DNA samples were analyzed by next-generation sequencing [NGS] gene panel and Sanger sequencing


Results: Five different variants were identified in COLlAl and COL1A2, including two variants in COLlAl and three variants in COL1A2. Among the five causative COLlAl and COL1A2 variants, one novel variants, c.1081 G>A, was found in COL1A2, which was identified in two siblings


Conclusion: Our finding extends the variant spectrum of the COL1A2 gene and has important implications for genetic counseling of families. The NGS is a powerful molecular diagnostic strategy for Ol, a heterogeneous disorder


Subject(s)
Humans , Collagen Type I , Mutation, Missense , Siblings , Genetic Counseling , Sequence Analysis , Consanguinity
19.
EMHJ-Eastern Mediterranean Health Journal. 2016; 22 (6): 368-374
in English | IMEMR | ID: emr-181490

ABSTRACT

The study was conducted to determine the family, social and economic factors associated with deaths of children aged under 5 years. A registry-based nested case-control study was conducted of the deaths of all children aged under 5 years in Kohgilooyeh and Boyer-Ahmad Province in the Islamic Republic of Iran. For each death, two controls were randomly selected among children of the same age, sex and place of residence [186 cases and 372 controls]. Congenital abnormality [37.6%] and preterm birth [29.0%] were the two most frequent causes of death among children aged under 5 years. No vaccine-preventable disease was reported as the cause of death. The strongest associations were found with consanguinity of the parents [OR = 3.92; 95% CI = 2.27-6.85 for being first cousins in comparison with no family relation; P < 0.001] and with domestic violence to the mother during pregnancy [OR = 3.13; 95% CI = 1.60-6.17; P < 0.01]. The main causes of death of children aged under 5 years in the Province were congenital abnormality and prematurity


Subject(s)
Humans , Female , Male , Infant, Newborn , Infant , Child, Preschool , Child , Mortality, Premature , Congenital Abnormalities/epidemiology , Consanguinity , Case-Control Studies
20.
Journal of Taibah University Medical Sciences. 2016; 11 (3): 203-210
in English | IMEMR | ID: emr-180219

ABSTRACT

Objectives: Localized autosomal recessive hypotrichosis is a non-syndromic human hair loss disorder, affecting scalp, eyebrows and eyelashes, and other parts of the body. Six consanguineous families with this form of hair loss disorder were investigated at both the clinical and molecular levels


Methods: Linkage in six families with twenty-one affected members was tested by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci including localized autosomal recessive hypotrichosis [LAH] 1, 2 and 3. Sequence analysis of the entire coding and splice sites of the gene DSG4 was performed to search for the disease-causing mutation


Results: Genotyping established linkage in families to the DSG4 gene at LAH1 locus on chromosome 18q21.1. Sequence analysis detected an intragenic deletion mutation [Ex5_8 del] in affected members of all six families


Conclusion: Identification of recurrent mutation in six additional Pakistani families strengthens the body of evidence that this is an ancestral mutation that is widespread among different Pakistani ethnic groups


Subject(s)
Humans , Sequence Deletion , Genetic Association Studies , Desmogleins/genetics , Consanguinity
SELECTION OF CITATIONS
SEARCH DETAIL