Diagnosis and Treatment of Familial Hypokalemic Periodic Paralysis with Acidosis / 中山大学学报(医学科学版)

ObjectiveTo investigate the diagnosis and treatment of familial hypokalemic periodic paralysis with acidosis. MethodsThe proband's medical history， clinical manifestations， laboratory examinations and imaging characteristics were retrospectively analyzed， and prevalence situation of family members was investigated in detail. Next generation sequencing technology was used to detect the pathogenic gene loci related to periodic paralysis， and the relevant literatures were summarized. ResultsThe proband was definitely diagnosed as familial hypokalemic periodic paralysis. There was a heterozygous mutation in the SCN4A gene of the proband， which was c.2006G>A， resulting in amino acid changes R669H.The proband's grandfather， father and uncle shared the same variation. ConclusionsFamilial hypokalemic periodic paralysis with paroxysmal acidosis is rare， which is easily misdiagnosed as renal tubular acidosis. c 2006G>A mutation in SCN4A gene is the molecular basis of the disease in this family. The clinical phenotypes of different gene mutations are different， and gene screening is helpful for diagnosis and treatment.

Anti Colton-A Foeto-Neonatal Haemolytic Disesase: Diagnosis; Clinical Outcome and Family Study

The authors report a case of neonatal haemolytic disease (HDN) attributable to maternal allo immunization to a high frequency antigen present on paternal red blood cells which have been identified as Colton-a (Coa).The case seemed worthy of reporting not only for the relative rarity of HDN from anti Coabut for the rigorous approach followed in the immunohaematological follow-up of pregnancy and for the diagnostic effort expended in identifying the specificityof the antibody. A family study of ascendants, collaterals and descendants was also carried out using genotyping techniques.

Serological and molecular investigation of B (A) blood group and its transfusion strategy: A case report / 中国输血杂志

【Objective】 To study the serological and genetic characteristics of a case of B(A) blood group. 【Methods】 Serological and genetic ABO blood group typing were used to analyze the ABO subtype and family inheritance of the probands and her 8 family members. The B(A) blood type sample was used as the blood recipient, and the B-type and O-type donors were selected for cross-matching using microcolumn gel anti-human globulin method to evaluate the blood transfusion strategy. 【Results】 5 out of 9 family blood samples were B(A) phenotype, carrying B(A)04 allele. Among them, 1 was B(A)04/O1 type, and 4 were B(A)04/B type. The primary blood matching of B(A) blood type samples with type B and O recipients were all negative. 【Conclusion】 A total of 5 cases of B(A)04 blood type were found in this family investigation, and there were differences in serological manifestations. Washed RBCs with B and O type can be used for B(A) blood type transfusion, and type B suspended RBCs can be considered in case of emergency.

Molecular Mechanism and family research of a pedigree with B(A).06 subtype / 中华医学遗传学杂志

Objective@#To explore the serological and genotypic characteristics of a pedigree with B(A).06 subtype.@*Methods@#Serological methods was used to identify the ABO phenotypes. Exons 6 and 7 of the ABO gene and flanking regions were subjected to direct sequencing and TA clonal sequencing in order to determine the genotype of individuals with inconsistent results for forward and reverse serological typing.@*Results@#Among 12 individuals from 4 generations, 5 were identified with a AwB phenotype, along with a c. 803C>G mutation in exon 7 of the B allele, which was named as B(A).06. The B(A).06/O.01.01 phenotype may be easily missed due to its weak anti-A antibody in the serum upon initial serological test.@*Conclusion@#A B(A).06 subtype family was identified. The serological phenotype of individuals carrying the B(A).06 allele may be affected by the opposite DNA strand.

Sexual transmission of American trypanosomiasis in humans: a new potential pandemic route for Chagas parasites

BACKGROUND The Trypanosoma cruzi infection endemic in Latin America has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. We hypothesised that the sexual transmission of T. cruzi contributes to the ongoing spread of Chagas disease. OBJECTIVES A short-term longitudinal study was conducted to evaluate this hypothesis. METHODS The study population comprised 109 subjects from four families, among whom 21 had been diagnosed with acute Chagas disease by direct parasitological analysis. Blood mononuclear cells and serum samples were obtained from each study subject once per year for three consecutive years. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence serological examinations were used to detect specific T. cruzi antibodies. Polymerase chain reaction of T. cruzi DNA revealed 188-nucleotide bands, which hybridised to a specific radiolabelled probe and were confirmed by cloning and sequencing. RESULTS Three independent assessments at different time points revealed T. cruzi nuclear DNA footprints in 76% (83/109) of the study population with active infection. In contrast, the ELISA and indirect immunofluorescence assays detected the T. cruzi antibody in 28.4% (31/109) of the study samples. Moreover, the semen from 82.6% (19/23) of subjects people revealed harboured the 188- bp base pair T. cruzi footprint. Interestingly, the ejaculates of nuclear DNA-positive Chagas patient transmitted the T. cruzi upon peritoneal injection or infusion in the vagina of mice, and amastigotes were detected in the skeletal muscle, myocardium, vas deferens, and uterine tube. MAIN CONCLUSIONS T. cruzi infections can be transmitted from females or males to naïve mates through intercourse, and progeny showed discrepancies between the ratios of nuclear DNA footprints and specific antibody that can be explained by the tolerance attained during early embryo growth. Additional studies are needed to develop drugs to eradicate the infections. Additionally, the importance of a vigorous education, information, and communication program to prevent sexually transmitted Chagas disease in humans cannot be underemphasised.

Mothers-Offspring Resemblance in Intelligence and Its Relationship to Socioeconomic Status / Semelhança Entre Mães e Filhos em Inteligência e sua Relação com o Nível Socioeconômico / Semejanza Entre Madres e Hijos e su Relacion con el Nivel Socioeconómico

Abstract: Kinship studies have shown that most cognitive ability variances are attributable to genotypic variance. Additionally, kinship correlations are generally increased when tasks that are highly g loaded are considered, a result known as the "Jensen effect". Alternatively, some studies have suggested socioeconomic status as an important factor for explaining differences in cognition. The present study investigated these premises in a sample of 141 mothers (mean age = 36.6; SD = 6.0) and their offspring (53.2% girls; mean age = 11.0; SD = 2.1). The Standard Progressive Matrices of Raven (mothers and offspring) and six other cognitive measures (offspring only) were administered. The findings suggested evidence of g heritability (Jensen effect), which is consistent with published literature on intelligence. However, kinship correlation coefficients were lower (.041 to .177) when compared to other published findings. Finally, the difference between the mother's IQ score and that of her child was influenced by SES and mother's education level.

Resumo: Estudos familiares demonstram que grande parte da variância das habilidades cognitivas é atribuída à variância genotípica. Além disso, correlações de parentesco possuem, geralmente, maiores valores quando as tarefas são altamente carregadas de g, fenômeno conhecido como "efeito Jensen". No entanto, em outra linha de investigação, estudos sugerem que o nível socioeconômico é um fator importante para explicar as diferenças cognitivas. O presente estudo investigou essas premissas em uma amostra de 141 mães (idade media = 36,6; DP = 6,0) e seus filhos (53,2% meninas;idade média = 11,0; DP = 2,1). Administrou-se as Matrizes Progressivas de Raven (em mães e filhos) e seis outras medidas cognitivas (nos filhos). Os resultados sugeriram uma evidência de herdabilidade em g (efeito Jensen). No entanto, os coeficientes de correlações familiares foram menores (0,041 a 0,177) a outros comumemente publicados. Por outro lado, a diferença entre os scores de QI das mães e de seus filhos foi influenciada pelo nível socioeconômico (NSE) e pelo nível de escolaridade da mãe. No geral, advoga-se por uma interação gene x ambiente das diferenças de habilidades cognitivas dependente do contexto socio-econômico.

Resumen: Los estudios familiares han mostrado que gran parte de la varianza de las habilidades cognitivas es dada por la varianza genotípica. Además, las correlaciones de parentesco generalmente tienen mayor valor cuando las tareas demandan alto g, fenómeno conocido como "efecto Jensen". Sin embargo, considerando otra línea de investigación, los estudios sugieren que el nivel socioeconómico es un factor importante para explicar las diferencias cognitivas. El presente estudio investigó estas premisas en una muestra de 141 madres (edad media = 36,6; DT = 6,0) y sus hijos (53,2% niñas; edad media = 11,0; DT = 2,1). Fue administrado las Matrices Progresivas de Raven (en madres y niños) y otras seis medidas cognitivas (en niños). Los resultados sugieren evidencia de herdabilidad en g (efecto Jensen), hallazgo consistente con la literatura. Con todo, los coeficientes de correlación de parentesco fueron inferiores (0.041 a 0.177) en comparación con otras publicaciones. Finalmente, la diferencia entre las puntuaciones de CI de madres y sus hijos fue influenciado por el nivel socioeconómico (SES) y el nivel educativo de la madre.

Estudio generacional en familias con distrofia corneal endotelial de Fuchs / Generational study conducted in families with Fuchs' endotelial corneal dystrophy

OBJETIVOS: identificar la presencia de rasgos clínicos de distrofia corneal endotelial de Fuchs en familiares de pacientes con este diagnóstico. MÉTODOS: se realizó un estudio observacional, descriptivo y transversal de 15 familias trigeneracionales de pacientes con distrofia corneal endotelial de Fuchs, captados en consulta de córnea del Instituto cubano de Oftalmología "Ramón Pando Ferrer" del año 2008 al 2011. La muestra quedó constituida por un total de 78 pacientes. Se utilizaron planillas de recolección de datos para estudiar las siguientes variables de interés: gutas corneales según grados, clasificación clínica, edad, sexo y grado de parentesco según árbol genealógico familiar. Se resumieron las variables cualitativas utilizando frecuencias absolutas y relativas porcentuales. RESULTADOS: del total de descendientes directos, el 44,1 % presentó gutas en su córnea. El 34,6 % de los pacientes estudiados presentaron la enfermedad y el 23,1 % córnea guttata. La distrofia y la córnea guttata se constataron más en el sexo femenino, con mayor incidencia en mayores de 60 años para los primeros. Los descendientes del primer nivel evidenciaron más afectación corneal que los de segundo nivel, con el 75,9 y el 23,5 % respectivamente. Todas las familias presentaron miembros afectados en su descendencia. CONCLUSIONES: la mayor parte de las familias de pacientes con distrofia corneal endotelial de Fuchs presentan cambios endoteliales en las córneas, por lo que estas deben ser incluidas en el estudio con fines diagnósticos y preventivos.

OBJECTIVE: to identify clinical features of Fuchs' endothelial corneal dystrophy in relatives of patients with this diagnosis. METHODS: bservational, descriptive and transversal study of 15 three- generation families of those patients with Fuchs' endothelial corneal dystrophy who went to the cornea consultation of the "Ramón Pando Ferrer", Cuban Institute of Ophthalmology from 2008 to 2011. The sample was made up of 78 patients. Data collection forms were used to study the following variables of interest: Cornea Guttata by degree, clinical classification, age, sex and degree of relationship as family tree. Qualitative variables were summarized using percentage absolute and relative frequencies. RESULTS: of the total number of direct descendants, 44,1 % had cornea guttata; 34,6 % of the patients presented with Fuchs' endothelial corneal dystrophy and 23,1 % of them had cornea guttata. Dystrophy and cornea guttata were found more frequently in females, with the highest incidence of the former in patients over 60 years. First degree descendants showed more corneal involvement than the second degree ones (75,9 and 23,5 %, respectively). All the families had offspring affected by the disease. CONCLUSIONS: most of the members of the families suffered corneal endothelial changes, so they should be included in the study for diagnostic and preventive purposes.

A family study of mandibuloacral dysplasia with type A lipodystrophy / 临床儿科杂志

Objective To study the gene mutations and clinical features of mandibuloacral dysplasia with type A lipodystrophy (MADA) in a Chinese family. Methods The information of 5 family members including 2 siblings suspected atyp-ical progeria was assembled. Genomic DNA was extracted from peripheral blood of 5 family members, the 12 exons of LMNA gene were ampliifed by PCR and then the PCR products were directly sequenced and analyzed by using Blast software online. The SIFT and PolyPhen-2 software were used to predict the harmfulness of mutations. Results The 2 siblings were clinically diagnosed as MADA. Heterozygous c.1579C>T (p.Arg527Cys) and c.1583C>T (p.Thr528Met) mutations were detected in this family. The father carried c.1583C>T (p.Thr528Met) mutation, the mother carried c.1579C>T (p.Arg527Cys) mutation, and their normal daughter were all heterozygous carriers with c.1583C>T (p.Thr528Met) mutation. Compound heterozygous c.1579C>T (p.Arg527Cys) and c.1583C>T (p.Thr528Met) mutations in 2 siblings led to MADA. The MADA showed an autosomal re-cessive inheritance pattern in this family. Conclusions The 2 siblings with MADA in this family were caused by compound heterozygous mutations in LMNA gene.

Familial Study of Paracentric Inversion in Chromosome 3p.

Aims: To describe the familial occurrence of paracentric inversion of chromosome 3. Presentation of Cases: Patient 1: Female, Caucasian, born in Southeast of Brazil, 7 years old. Born at term and asphyxia. Developmental delay; aggressive behavior and tendency toward isolation. Prominent forehead, discrete epicanthal folds, down-slanting palpebral fissures, long philtrum and hypermobility of the four limbs. Karyotype: 46,XX,inv(3)(p13p25). Patient 2: Female, Caucasian, born in Northeast of Brazil, 3 years old. Born prematurely by cesarean section, pelvic presentation and asphyxia. Severe developmental delay. Microcephaly, bilateral convergent strabismus, epicanthal folds, wide nasal bridge, micrognathia, high arched palate and nasolabial hemangioma, low set ears, hypoplastic nipples, nucal café-au-lait spots, deep plantar fold. Dysgenesis of the corpus callosum. Karyotype: 46,XX,inv(3)(p13p25). Patient 3: Male, Caucasian, born in Southeast of Brazil, 5 years. Born at term, by cesarean section, cephalic presentation. Developmental delay and flexor spasms. Dolichocephalic skull, prominent forehead, ocular hypertelorism, epicanthal folds, disproportioned and low set ears, single palmary crease in the right hand, large and elongated thumbs, hypotonia, and recurrent acute otitis. Karyotype: 46,XY,inv(3)(p13p25). Discussion: Patients presented developmental delay and dysmorphic features, but the relatives that presented the same inversion were asymptomatic. Carriers seem to have a normal reproductive fitness, without differences between males and females. Conclusion: The chromosomal rearrangements, especially balanced chromosomal alterations provide an opportunity to broaden the understanding of the structure and functional organization of chromosomes and to offer better genetic counseling for the families.

Six Years' Experience Performing ABO Genotyping by PCR-direct Sequencing / 대한수혈학회지

BACKGROUND: ABO genotyping is essential for resolving ABO grouping discrepancy and for determinating ABO subgroups. Most clinical samples, including suspected inherited subgroups and acquired variant phenotypes, can be determined by PCR-sequencing of exons 6 and 7 in the ABO gene. Here, we describe our six years' experience performing ABO genotyping by PCR-direct sequencing. METHODS: We conducted a retrospective investigation of serological and genotypical data from 205 samples (158 patients and 47 of their family members) of patients who were referred to the Molecular Genetics Laboratory at Chonnam National University Hwasun Hospital for ABO genotyping between January 2007 and July 2012. ABO genotyping was performed on all samples with PCR-direct sequencing of exons 6 and 7 in the ABO gene; the standard serologic tests were also performed. RESULTS: The frequency of phenotypes consistent with their genotypes was 70.8% (112/158 cases) and the A2B3 phenotype with the cis-AB01 allele was the most common (31.0%, 49 cases) among them. The frequency of phenotypes inconsistent with their genotypes was 29.1% (46/158 cases) and the A1B3 phenotype was the most frequently recovered case (5.1%, 8 cases). Family study showed differential phenotype expression depending on the co-inherited ABO allele in five families with the B306, cis-AB01, Ael02, Aw14, or B305 allele and also showed a typical inheritance of a chimera with A102/B101/O04. CONCLUSION: We propose that ABO genotyping using PCR-direct sequencing is useful for the resolution of ABO discrepancies and for the investigation of ABO subgroups based on six years' experience. In addition, family study for analysis of phenotypic patterns of ABO subgroups is also crucial to ABO genotyping.

Six Years' Experience Performing ABO Genotyping by PCR-direct Sequencing / 대한수혈학회지

BACKGROUND: ABO genotyping is essential for resolving ABO grouping discrepancy and for determinating ABO subgroups. Most clinical samples, including suspected inherited subgroups and acquired variant phenotypes, can be determined by PCR-sequencing of exons 6 and 7 in the ABO gene. Here, we describe our six years' experience performing ABO genotyping by PCR-direct sequencing. METHODS: We conducted a retrospective investigation of serological and genotypical data from 205 samples (158 patients and 47 of their family members) of patients who were referred to the Molecular Genetics Laboratory at Chonnam National University Hwasun Hospital for ABO genotyping between January 2007 and July 2012. ABO genotyping was performed on all samples with PCR-direct sequencing of exons 6 and 7 in the ABO gene; the standard serologic tests were also performed. RESULTS: The frequency of phenotypes consistent with their genotypes was 70.8% (112/158 cases) and the A2B3 phenotype with the cis-AB01 allele was the most common (31.0%, 49 cases) among them. The frequency of phenotypes inconsistent with their genotypes was 29.1% (46/158 cases) and the A1B3 phenotype was the most frequently recovered case (5.1%, 8 cases). Family study showed differential phenotype expression depending on the co-inherited ABO allele in five families with the B306, cis-AB01, Ael02, Aw14, or B305 allele and also showed a typical inheritance of a chimera with A102/B101/O04. CONCLUSION: We propose that ABO genotyping using PCR-direct sequencing is useful for the resolution of ABO discrepancies and for the investigation of ABO subgroups based on six years' experience. In addition, family study for analysis of phenotypic patterns of ABO subgroups is also crucial to ABO genotyping.

Genetic power of a brazilian three-generation family with generalized aggressive periodontitis. II

The genetic power of a Brazilian three-generation family with generalized aggressive periodontitis (GAgP) has been reported. The empirical logarithms of the odds (LOD) score thresholds for genetic linkage analysis of complex diseases proposed by Haines rely on confirmation from independent datasets. This study estimated the power of another large Brazilian family with GAgP for future linkage analysis. The three-generation family was seen at the Dental School of the Federal University of Bahia. Following the previously described methodology, full-mouth periodontal probing at 6 sites/tooth was performed in all 19 family members. Six out of 12 siblings were affected with GAgP. All affected family members were non-smokers and did not present diabetes or any other systemic condition or consanguinity. A parametric simulation (?=0) was performed on 100 replicates using the statistical software SLINK for linkage analysis. There was maximum expected LOD scores of 3.75 and 3.45 at penetrance rate F=0.98, and both studied phenocopy rates P=0.0 and P=0.02, respectively. The power of the study increased with the increase of the adopted penetrance rates in both studied phenocopy rates. The studied Brazilian three-generation family showed statistical power for future genetic linkage analysis of candidate genes to GAgP.

O poder genético em uma família brasileira de três gerações com periodontite agressiva generalizada (PAgG) foi reportado. Os valores dos escores logarítmicos (LOD) empíricos para análise genética de ligação de doenças complexas propostos por Haines se baseam na confirmação em conjuntos de dados independentes. O objetivo deste estudo foi de estimar o poder de uma nova grande família com PAgG para futura análise de ligação. A família de três gerações foi vista na Faculdade de Odontologia da Universidade Federal da Bahia. De acordo com metodologia previamente descrita, sondagem periodontal em 6 sítios/dente foi realizada em todos 19 membros da família. Seis de 12 irmãos apresentaram PAgG. Todos os membros afetados da família eram não fumantes, não apresentaram diabetes ou qualquer condição sistêmica ou consangüinidade. Uma simulação paramétrica (?=0) foi realizada em 100 réplicas usando software estatístico SLINK para análise de ligação. Houve escore LOD esperado máximo de 3,75 e 3,45 no valor de penetrância F=0,98 em ambas razões de fenocópia estudadas P=0,0 e P=0,02, respectivamente. O poder do estudo aumento com o aumento do grau de penetrância adotado em ambas razões fenotípicas estudadas. A família brasileira de três gerações estudada mostrou poder estatístico para futura análise de ligação genética de genes candidatos para PAgG.

Heritability estimation of conventional cardiovascular disease risk factors in Asian Indian families: The Calcutta family study.

The genetic causes of the components of cardiovascular disease (CVD) risk factors and their intercorrelation are indeed complex and only partly understood. Keeping this view in mind, the present work was undertaken to estimate the heritability of conventional CVD risk factors using family study method. A total of twenty-four nuclear families inhabiting in Calcutta and adjacent areas was chosen randomly. Up to first degree relatives including father, mother and other sibs of the proband were considered as participants in the study. Anthropometric measures namely height, weight, waist circumference as well as skinfold thickness at biceps, triceps, subscapular and suprailiac were obtained using standard techniques. Body mass index (BMI), percentage of body fat (PBF), fat mass (FM), waist-hip ratio (WHR), sum of four skinfolds (SF4 ), arm muscle circumference (AMC), arm muscle area (AMA), arm fat area (AFA), systolic (SBP) and diastolic blood pressure (DBP) were also considered. To estimate’heritability’ in the study, the mid parent-offspring model was used where’heritability’ (h2 ) was equivalent to regression co-efficient (b). The regression sum of square (RSS) and total sum of square (TSS) ratio was also calculated both for mid parent-offspring and single parent-offspring. This ratio was considered as a measure of’heritability’ in the study with consideration that RSS is the variation due to genetic factor and the TSS is due to genetic and other additive factor. It was observed that the estimated heritability for BMI ranges from 0.69 to 0.31 using mid-parent off spring model while the range using single parent-offspring model was from 0.40 to 0.16. The range of heritability for SBP in mid parent-offspring model was 0.16 to 0.44 and 0.05 to 0.54 for single parent-offspring model. To conclude, it seems reasonable to argue that in the study a moderate to high h2 was evident for body fat level, body composition and blood pressure measures which indicate a moderate to high aggregation of gene(s) in the family.

Genetic power of a Brazilian three-generation family with generalized aggressive periodontitis

Aggressive periodontitis is a multifactorial disease with strong familial aggregation. Genetic linkage analysis is a method to localize causative or predisposing genes along the chromosome, thus helping to unravel important pathogenic pathways. Prior to applying this method, however, it is essential to estimate the power of the study design. The aim of this study was to estimate the power of a large Brazilian family with generalized aggressive periodontitis (GAgP) for future linkage analysis. A three-generation family was seen at the Dental School of the Federal University of Bahia. A full-mouth periodontal probing at 6 sites/tooth was performed in all 23 family members. Five out of 10 siblings were affected with GAgP. A parametric simulation (? = 0) was performed on 100 replicates using the statistical software SLINK for linkage analysis. The linkage LOD score criteria for complex diseases described by Haines was adopted. There was maximum expected LOD scores of 3.56 and 3.48 at penetrance rate F = 0.98, and both studied phenocopy rates p=0.0 and p=0.02, respectively. The analyzed family showed statistical power for future genetic linkage analysis of candidate genes to GAgP.

Periodontite agressiva é uma doença multifatorial que apresenta forte agregação familiar. Análise de ligação genética é um método que localiza genes que causem ou predisponham doenças ao longo do cromossomo e pode ser útil na descoberta de importantes mecanismos patogênicos. No entanto, antes de se realizar uma análise genética de ligação, é essencial estimar o poder do estudo delineado. O objetivo deste estudo foi estimar o poder de uma grande família apresentando periodontite agressiva generalizada para futura análise genética de ligação. Uma família de três gerações (23 membros) que procurou por tratamento periodontal na Faculdade de Odontologia da Universidade Federal da Bahia foi analisada. Em todos os membros familiares foi realizado um exame periodontal completo em seis sítios/dente em todas as unidades dentais presentes por um único examinador. Dos dez irmãos, cinco apresentaram a periodontite agressiva generalizada de acordo com o sistema de classificação da Academia Americana de Periodontia 1999. Uma simulação paramétrica (? = 0) foi realizada em 100 repetições com o uso do software SLINK para ligação genética. O escore logarítmico LOD descrito como critério para doenças complexas (poligênicas ou multifatoriais) por Haines foi adotado. Em nosso estudo foi encontrado um LOD esperado máximo de 3,56 e 3,48 na razão de penetrância F=0,98 nas duas razões de fenocópia estudadas p=0,0 e p =0,02, respectivamente. A família analisada mostrou ter poder estatístico suficiente para futura análise de ligação genética de genes candidatos para periodontite agressiva generalizada.

Enfermedad Celiaca en familiares de primer grado: Familia nuclear con 5 miembros afectados

La Enfermedad Celíaca (EC) se define como una enteropatía mediada inmunológicamente por una sensibilidad permanente al gluten en individuos genéticamente susceptible. Estudios epidemiológicos en América y Europa reportan una prevalencia aproximada entre 0,5 a 1% entre la población general. En los Estados Unidos solo de 10 a 15% o menos de estos individuos son diagnosticados y tratados. Existe una fuerte susceptibilidad genética en el desarrollo de EC, como lo confirma la elevada concordancia observada en gemelos monocigóticos, que llega hasta un 75%. Se encuentra una elevada prevalencia en familiares de primer y segundo grado que oscila entre 4-12%, esta relación es debida, en gran parte, a la existencia de una importante base genética condicionada por la presencia de antígenos de clase HLA-II (DQ2 y DQ8). Se presenta el caso de una familia nuclear constituida por 5 miembros, en la cual se lleva a cabo el screening para EC a partir de un caso índice, obteniendo como resultado que el 100% (5/5) del grupo familiar se encuentra positivo desde el punto de vista serológico para EC (Anticuerpos Anti TTG fracción Ig A), siendo necesario resaltar que el 40% de este grupo familiar se encuentra asintomático al momento del diagnostico, tanto desde el punto de vista gastrointestinal como no gastrointestinal. Consideramos, que es imperativo el estudio de las familias donde sea detectado al menos un caso de EC, debido a que la prevalencia de la penetración en un grupo familiar puede alcanzar hasta el 100%.

Celiac disease (CD) is an immune enteropathy mediated by a permanent sensitivity to gluten in genetically susceptible individuals. Previous studies in Europe and America reported prevalence estimated between 0.5 to 1% among the general population. In the United States only 10 to 15% or less of these individuals are diagnosed and treated. There is a strong genetic susceptibility in the development of CD, as confirmed by the high concordance observed in monozygotic twins, which reaches up to 75%. There is a high prevalence in first and second degree relatives that ranges between 4-12%; this relationship is due, in large part, to the existence of a significant genetic basis conditioned by the presence of HLA antigens class-II (DQ2 and DQ8). A case of a nuclear family consisting of 5 members was screened for CD from an index case, which resulted in 100% (5 / 5) of the family, was positive for serological CD (TTG Antibodies Ig fraction A). We have to address that 40% of this family are asymptomatic at diagnosis, both in terms of gastrointestinal and non gastrointestinal symptoms. We believe that the study of a family group in which at least one of the members is diagnosed with CD is imperative; due to the high prevalence level of household penetration CD, which can reach, up to 100%.

A Korean Family with Wilson Disease Occurred in Two Consecutive Generations / 대한진단검사의학회지

Wilson disease (WD) is one of the most common inborn errors of metabolism characterized by degenerative changes in the brain, liver and kidney dysfunction, and Kayser-Fleischer rings due to toxic accumulation of copper. We investigated a Korean family with WD occurred in two consecutive generations. The proband, a 14-yr-old girl, was noticed to have abnormal liver function on a routine health examination at school and was diagnosed of having WD by further laboratory tests and liver biopsy. Molecular genetic analysis of ATP7B gene demonstrated that she was homozygous for Ala-874Val mutation, one of the three common mutations in Korean patients with WD. Further study for her family members revealed that the proband's father, a paternal uncle, and the youngest sister were compound heterozygous for Ala874Val and Asn1270Ser mutations of the ATP7B gene. In addition, the proband's mother and a younger sister were heterozygous carriers of Ala874Val mutation. Therefore, WD occurred in two consecutive generations due to a WD father and a heterozygous mother. Actually, abnormal results on liver function tests were found in the proband's father and a paternal uncle a few years ago but a diagnosis of WD has not been made. Therefore, although WD has been thought to be uncommon in Korea, it should be considered in a differential diagnosis of patients exhibiting abnormal liver function with unknown cause.

Heterogeneidad clínica y genética de la retinosis pigmentaria: Importancia del estudio familiar y del tratamiento precoz. A propósito de una familia / Clinical and genetical heterogeneity of retinitis pigmentosa: Importance of the family study and of early treatment. Apropos of a family

Conocida es la heterogeneidad genética de la retinosis pigmentaria considerada por diferentes autores como un grupo de enfermedades hereditarias que se deben a distintas mutaciones y se transmiten por diferentes patrones mendelianos de herencia que se manifiesta en general, con un cuadro clínico similar en sus características fundamentales. Notable es también su heterogeneidad desde el punto de vista clínico pues distintos genotipos se corresponden con distintos fenotipos, pero incluso entre los individuos afectos de la misma mutación pueden ser manifiestas las diferencias existentes en diversos aspectos clínicos de la enfermedad, por ello se reconoce por los investigadores dedicados a su estudio lo indispensable de un adecuado estudio familiar para un diagnóstico correcto, sobre todo desde el punto de vista genético. Se presenta una familia clasificada inicialmente como afecta de retinosis pigmentaria típica autosómica recesiva que luego de la pesquisa clínico familiar en cascada se reclasificó como de herencia autosómica dominante. Se evidenció la importancia del exhaustivo estudio familiar y del tratamiento quirúrgico precoz.

It is known the genetical heterogeneity of retinitis pigmentosa considered by different authors as a group of hereditary diseases resulting from different mutations that are transmitted by different Mendelian patterns of inheritance that are generally manifested by a clinical picture that is similar in its fundamental characteristics. Its heterogeneity is also remarkable from the clinical point of view, since different genotypes correspond to various phenotypes, but even among the individuals affected with the same mutation the differences existing in dissimilar clinical aspects of the disease may be manifested. That's why, the investigators devoted to its study recognize that it is indispensable to conduct a family study to have a correct diagnosis, mainly from the genetical point of view. A family initially classified as affected by recessive autosomal typical retinitis pigmentosa that after the cascade clinical family screening was reclassified as dominant autosomal inheritance, was presented. The importance of the in-depth family study and of the early surgical treatment was evidenced.

Family Study of TAP Gene Polymorphism and HLA-TAP Haplotypes in Koreans

BACKGROUND: TAP1 and TAP2 are two ABC transporter genes located within the class II region of the human MHC. Their protein products form a heterodimer whose function is to transport peptides from the cytoplasm into the endoplasmic reticulum. This study was performed to examine the polymorphism of TAP genes and the distribution of HLA-TAP haplotypes in the Korean population through family analysis. METHODS: The subjects used in this study were 50 healthy Korean families consisting of 233 individuals. TAP1 (codons 333 and 637) and TAP2 (codons 379, 565, 577, 651, 665, and 687) typings were carried out by the PCR-restriction fragment length polymorphism (RFLP) method. HLA-DRB1 and DQB1 genotyping results from a previous study were used for HLA-TAP haplotype analysis. RESULTS: The number (gene frequency) of TAP1 and TAP2 alleles detected were 3 for TAP1 (A 81.5%, B 17.0%, and C 1.5%) and 8 for TAP2 (A1 32.0%, A2 12.5%, B 34.0%, Bky2 6.5%, C 7.0%, D 3.0%, E 4.5%, and G 0.5%). Eleven TAP1-TAP2 haplotypes were observed with frequency 1%, among which 4 haplotypes (A-B, B-A1, A-Bky2, and C-E) showed weak but significant positive linkage disequilibrium (P<0.05). When DRB1-DQB1 haplotypes were extended to TAP1 and TAP2 loci, much diversification of haplotypes was observed: 19 different DRB1- DQB1 haplotypes formed 58 different haplotypes extended to TAP1 and TAP2 loci. These results add more evidence to the view that recombination hotspot is present within and around TAP gene region. CONCLUSION: The allele frequencies of TAP1 and TAP2 genes and the distribution of TAP1-TAP2 and HLA-TAP haplotypes were studied in Koreans based on a family study.

Molecular genetics analysis of a Chinese family carrying triple HLA-A antigen / 中国输血杂志

Objective A rare HLA phenotype carrying three HLA-A antigens, A2, A11.2 and A24, was identified in a potential bone marrow donor SZHD1. Methods To determine molecular basis of this phenotype the HLA-A gene fragments from this donor and his family members were cloned and sequenced. Results Sequencing analysis indicated that the donor carries an unusual HLA haplotype, A*1102, A*24020101; B*38; DRB1*15. Conclusions Other four family members were found to carry this haplotype, which as a Mendelian gene was segregated and stably transmitted through three generations. This is a first example of a family carrying triple HLA-A antigens to the best of our knowledge.

A case of i Phenotype Siblings with Congenital Cataract / 대한수혈학회지

We report a two-generation Korean family in which 2 siblings have congenital cataract and phenotype i. This report is a first case in Korean people and shows the evidence suggesting the linkage of Ii blood group with a recessive form of congenital cataracts.