Research progress of genetic testing in male infertility / 中华检验医学杂志

About 15% of the world's population at child-bearing age suffer from infertility. After cancer and cardiovascular and cerebrovascular diseases, the infertility will become the third-largest intractable disease. Among the causes of infertility, male factors account for about half. As a main male factor, genetic factor has become the focus of reproductive research in recent years. Therefore, to formulate a corresponding diagnosis and treatment scheme for male infertility, accurate genetic testing is needed. It is an effective means to meet the demand of high fertility and solve the problem of population decline in current society.

Genetic etiology analysis of 420 children with neurodevelopmental disorders / 中华实用儿科临床杂志

Objective@#To investigate the genetic etiology of neurodevelopmental disorders (NDD), and to provide a theoretical basis for its genetic counseling, family risk evaluation and prenatal diagnosis.@*Methods@#Karyotype analysis and chromosome microarray analysis (CMA) were conducted of the data from 420 children diagnosed accor-ding to NDD diagnostic criteria at Maternal and Child Health Hospital of Hunan Province from January 2016 to December 2018.@*Results@#Among the 420 cases, 14 cases (3.33%, 14/420 cases) with global developmental disabilities/intellectual disabilities (GDD/ID) had chromosomal abnormalities.The location of chromosome breakpoints and the range of deleted or duplicated fragments in 13 cases were further determined by using CMA.In this study, pathogenic copy number variations (CNVs) were detected in 61 children (14.52%, 61/420 cases), which included 31 cases (50.82%, 31/61 cases) of known syndromes, including Angelman/Prader-Will syndrome (8 cases), Williams syndrome (3 cases), Phelan-McDermid syndrome (3 cases) and other 13 syndromes, and 30 cases with clinically significant pathogenic CNVs.Additionally, by the combination of CMA and fluorescence in situ hybridization (FISH), a family were diagnosed with mental retardation caused by 10q26 and 12p13 occult rearrangement.@*Conclusions@#Chromosomal abnormalities and genomic microdeletion/duplication are the primary genetic causes for children with NDD.Combination of karyotype analysis, CMA and FISH can provide definite etiological diagnosis for these children, which has important clinical signi-ficance for the treatment of children and guidance of their parents′ reproduction.

Comparative study of copy number variation sequencing and karyotype analysis in detection of chromosome abnormality / 西安交通大学学报(医学版)

Objective: To explore the clinical application of copy number variation sequencing (CNV-seq) and karyotype analysis in detection of chromosome abnormality. Methods: Chromosome of 42 patients was analyzed by karyotype analysis and CNV-seq. The advantages and limitations of the two methods were observed and compared. Results: We detected 7 cases of copy number variation by CNV-seq and the case detection rate was 16.67%. We detected cases of chromosomal anomalies by karyotype analysis, which included 6 cases of structural chromosome aberration and 2 cases of chromosome numerical abnormality. The case detection rate of karyotype analysis was 19.04%. Moreover, 4 cases of chromosome polymorphism were analyzed. Conclusion: CNV-seq can be applied in examining the abnormal chromosome number and structural aberrations, especially in providing clinically significant cytogenetic information that is difficult to be determined by karyotype analysis. It can also analyze chromosome microdeletion and microduplication syndrome with a chromosome resolution of 0.1 Mb. However, CNV-seq fails to identify balanced chromosomal translocation and inversion. Therefore, a combination of karyotype analysis and CNV-seq will provide accurate clinical diagnosis for patients with chromosome abnormality.

A Rare Case of a Male Infant with Down-Turner Syndrome and Review of Cases

@#Individuals with double aneuploidy of Down-Turner syndrome are very rare and to date, fewer than 50 cases have been reported, worlwide. We report a case of a male infant who presented with dysmorphic features of upslanting eyes, flat nasal bridge, wide spaced nipples and macroglossia. Based on the clinical features, he was diagnosed with Down syndrome. His peripheral blood sample was taken and sent for cytogenetic analysis for confirmation. Chromosome analysis of his lymphocyte cell culture revealed a mosaic pattern of double aneuploidy with monosomy X identified in 31 metaphases and trisomy 21 in 14 metaphases: (45,X[31]/47,XY,+21[14]). Further analysis with fluorescence in situ hybridization (FISH) using Vysis LSI SRY Spectrum Orange/CEP X Spectrum Green Probe and Vysis CEP Y Spectrum Aqua Probe and Vysis LSI 21 Spectrum Orange Probe performed on the cells (nuclei and metaphases) has confirmed the presence of the abnormal two cell lines (81% monosomy X and 19% trisomy 21) in the patient. Ultrasound investigations of his pelvic region showed normal testes and no evidence of uterus, ovary or vagina. To the best of our knowledge, this is the first Down-Turner syndrome reported in Malaysia. In conclusion, this case demonstrates the importance of Giemsa-banded karyotype and FISH analyses as diagnostic tools in identifying the chromosomal abnormality and determining the ratio of the normal:abnormal cells present in the patient. An annotated bibliography of earlier reported cases of Down-Turner with documented karyotyping is also included in this report.

Spondyloarthritis complicated with Turner syndrome / 中华风湿病学杂志

Objective To discuss the clinical manifestations and the characteristics of spondyloarthritis (SPA) complicated with Turners syndrome,in order to promote the understanding of this disease.Methods A case of ankylosingspondylitis complicated with Turner syndrome in our department was re-ported,7 similar reports of SpA complicated with Turner syndrome in recent chinese and foreign literatures were reviewed.Their symptoms,signs,laboratory examinations etc were analyzed.Results All 8 cases were female,the median age when patients first their visited doctors was 25 (10 to 34 years old),7 of them showed peripheral arthritis,4 of them showed remarkable low back pain and limited motion of the spine,1 showed pain in hip area,3 showed varus or valgus joint deformity,5 combined with osteoporosis.There were 3 chromosome karyotypes:① 45,XO;② 45,XO/46,XX;③ 45X/46,X,psu,idic (X).Per treatment,6 patients received treatment with sulfasalazine tablets and non steroidal anti-inflammatory drugs,1 combined with methotrexate tablets,5 received calcium and vitamin D,1 received treatment with bisphosphonates.For the treatment of Turner syndrome,2 received estrogen replacement therapy,1 received growth hormone therapy.Conclusion The characteristics of SpA complicated with Turner syndrome are remarkable peripheral arthritis,prone to osteoporosis.For treatment we should give consideration to both of the 2 diseases,especially pay attention to the treatment of calcium and vitamin D.

The genetic etiology research progress of oculo-auriculo-vertebral spectrum / 中华整形外科杂志

Oculo-auriculo-vertebral spectrum(OAVS)is one of common birth defects, which involves primarily optical, aural, maxillomandibular and spinal abnormal development. To date, the hereditary basis of OAVS has been generally accepted, but the responsible gene remains unclear. This article reviewed the possible etiology of OAVS in chromosome analysis, genome copy number detection, gene identification and mouse model, and analyzed the strategy for OAVS research.

The chromosome abnormality in forensic DNA test / 复旦学报（医学版）

Chromosome abnormality is a serious congenital disease,which was usually researched in genetic diseases and prenatal diagnosis.In recent years,some special STR profile and pseudo-exclusion case caused by abnormal chromosome are found in forensic DNA test.We reviewed several common chromosome abnormality contained trisomy syndrome,uniparental disomy and Chimera were reported in forensic medicine to provide reference for forensic DNA workers.

Ultrasonography-based diagnosis of fetal craniocerebral and neural tube malformation in early pregnancy / 实用医学杂志

Objective To evaluate the clinical effects of ultrasonography for structural examination in the diagnosis of fetal brain malformation and neural tube defects ( NTDs ) in early pregnancy . Methods A retrospective study was conducted to analyse 6 630 cases taking obstetric examination in Dongguan Maternal and Child Health Hospital from February 2014 to June 2015. The examination included a standardized ultrasound structural examination at 11-13 plus 6 weeks of pregnancy. The autopsied results of the induced fetus in early pregnancy from craniocerebral and neural tube structure malformation were investigated. All the cases were followed up concerning the outcomes and the malformation detection rate was calculated for analysis. Results The detection rates of exencephalus and anencephalus, holoprosencephaly, aphylly-holoprosencephaly, rachischisis, open spina bifida, and meningocele were 100%, 80%, 100%, 42.9%, 50% and 100%, respectively. The malformations which was missed in the early pregnancy but detected in the later gestational ages included:Dandy-Walker Syndrome, most of the non-open spina bifida, hypoplasia of the corpus callosum, foliaceous-holoprosencephaly and ventriculomegaly. Conclusions The structural examination using ultrasonography at early pregnancy is effective in the detection of severe open-neural tube defects. It′s worth generalizing in the cliical diagnosis but part of fetal malformations still need a further ultrasound examination in the mid-gestation or the later gestation.

Analysis of chromosome detection results in 1 237 infertile patients / 国际检验医学杂志

Objective To perform the chromosome detection in 1 237 infertile patients for analyzing the karyotypes results and investigating the relationship between infertility and chromosome abnormalities .Methods The peripheral venous blood samples in 1 237 infertile patients in our hospital from March 2010 to December 2014 were collected ,performed the lymphocyte culture ,ob‐tained cells ,fixed under hypotonic condition ,prepared the section and observed them by microscope after G‐banding treatment .Re‐sults Among 1 237 patients ,111 cases abnormal karyotypes were detected with the total abnormal detection rate of 8 .9% ,in which ,57 cases were sex chromosomes abnormality ,54 cases were euchromosomes abnormality .Conclusion Chromosome abnor‐mality is one of the important causes leading to primary infertility .Infertility caused by chromosome abnormalities is irreversible ,so the chromosome cytogenetic examination is especially important in the diagnosis and treatment process of infertile patients .

Esthesioneuroblastoma in a boy with 47, XYY karyotype / 소아과

Neuroblastomas are sometimes associated with abnormal constitutional karyotypes, but the XYY karyotype has been rarely described in neuroblastomas. Here, we report a case of an esthesioneuroblastoma in a boy with a 47, XYY karyotype. A 6-year-old boy was admitted to our hospital because of nasal obstruction and palpable cervical lymph node, which he first noticed several days previously. A polypoid mass in the right nasal cavity was detected through sinuscopy. Biopsy of the right nasal polyp was performed. Based on the result, the patient was diagnosed with a high-grade esthesioneuroblastoma. Nuclear imaging revealed increased uptake in both the right posterior nasal cavity and the right cervical IB-II space, suggesting metastatic lymph nodes. Cytogenetic analysis revealed a 47, XYY karyotype. Twelve courses of concurrent chemotherapy were administered. Three years after the completion of chemotherapy, the patient had had no disease recurrence. He manifested behavioral violence and temper tantrums, so we started methylphenidate for correction of the behavior.

Case Report of Ring Chromosome 13: 46,xx.r(13)(p13q34)/46,xx,dicr(13;13)(p13q34;p13q34).

Aims: To report a case of ring chromosome 13 in a female child. Presentation of Case: Female, Caucasian, born in Southeast of Brazil, 6 years old. Born by cesarean section, the physical examination at 6 years and 1 month old has shown: weight of 19.100 grams and 105 centimeters tall, developmental delay, bushy eyebrows, epicanthic folds and broad nasal bridge, cardiovascular and respiratory systems were normal and no abnormalities in the limbs. Chromosome analysis was performed by GTG banding of peripheral blood and the karyotype was 46,XX,r(13)(p13q34)[97]/46,XX,dic r(13;13)(p13q34;p13q34) [3]. Analysis of 100 metaphases following G-banding revealed 97% cells with a ring chromosome 13,3% with dicentric ring chromosome of two 13s. Aneuploidy was not detected. Her parents had a normal karyotype. Discussion: Some researchers relate the clinical presentation of ring chromosome 13 with the extension of the deleted chromosomal region and instability. Others suggested that phenotypes of patients can be categorized in groups, according to the breakpoint on 13q. Conclusion: The classification of cases in groups based on breakpoints and chromosomal instability is still inaccurate, with variable phenotypes. Thus, the analysis of a greater number of cases and molecular analysis are important to establish more precise correlation between genotype and phenotype.

Cytogenetic examination in 885 cytogenetic consultation cases / 重庆医学

Objective In order to get reference data for diagnosis of clinical genetic disease through analyzing chromosome ab‐normality types and rates in 885 patients who ask for cytogenetics consultation in recent years .Methods 324 newborns who asked for cytogenetics consultation because of high risk factors in down′s screening during pregnancy or found abnormality in physical ex‐amination after birth and 561 patients with history of spontaneous abortion ,infertility or fetal death ,growth or mental retardation , sexual abnormality were examined for karyotype analysis .Results 116 cases of chromosome abnormal karyotypes were detected , count for 13 .11% ,among which ,40 cases(34 .48% ) are chromosomal aberration .Chromosome abnormality types and rates are dif‐ferent in patients with different type of diseases .Conclusion Abnormalities in chromosome numbers and sex chromosome abnor‐mality account for the main causes of growth and mental retardation ,abnormalities of sexual differentiation and development ;but for couples suffered from spontaneous abortion ,polymorphism and structure abnormalities takes up the highest portion .

Gene array analysis in 56 cases of children with growth retardation / 临床儿科杂志

Objective To investigate the genetic basis of the children with growth retardation. Methods From January to October 2013, the 56 patients with growth retardation were enrolled in this study. Genomic DNA was extracted from peripheral blood and was analyzed with gene array chips. Results Abnormalities were found in 12 patients (6 cases of sex chromosome abnormalities and 6 cases of autosomal aberration) and the detection rate was 21.4%. Four patients had the copy-number variations of smaller than 2.5Mb in size which could not be found by karyotyping analysis. Conclusions SNP-array gene chip could be used in the genetic diagnosis of growth retardation.

Association between chromosome variations,abnormalities and male reproductive hormones level with spermatogenesis / 国际检验医学杂志

Objective To investigate the association between chromosome variations,abnormalities and male reproductive hor-mones level with spermatogenesis.Methods The chromosome karyotype,serum reproductive hormone including FSH,LH,T,PRL and E2,and semen were detected in 147 patients with male infertility or recurrent sponotaneous abortion.The results were per-formed the comparative analysis.Results Serum FSH,LH level and the incidence rate of azoospermia in the chromosome abnormal-ity group were significantly higher than those in the chromosome variation group and the normal group(P 0.05).Serum FSH,LH level and the incidence rate of azoospermia in the sex chromosome abnormality group were obviously higher than those in the autosomal abnormality group(P <0.05),the serum T level was signifi-cantly lower than that in the autosomal abnormality group(P <0.05).Conclusion The chromosome variation and abnormality are closely related with the reproductive hormones disorder and spermatogenetic function disorder.The obvious increase of serum FSH, LH level and obvious decrease of T level caused by sex chromosome variation and abnormality is one of the pathogenesis of oligo-spermia and azoospermia.

Síndrome de Patau o trisomía 13: reporte de caso / Patau syndrome or trisomy 13: a case report

RESUMEN Se presenta caso de síndrome de Patau diagnosticado ecográficamente a las 25 semanas de gestación y confirmado por cariotipo. Su desenlace fue fatal apenas nacido.

ABSTRACT We presents a Patau syndrome diagnosed by ultrasound at 25 weeks gestation and confirmed by karyotype. Its outcome was fatal shortly after birth.

The application of chromosome abnormality chip detection in male infertility / Aplicación de la detección de la anormalidad del cromosoma mediante biochips genéticos en la infertilidad masculina

OBJECTIVE: To discuss the application of microarray technology in the diagnosis of male infertility. METHODS: Sixteen loci, including a sex-determining region on the Y chromosome, were investigated by polymerase chain reaction (PCR) in infertile male patients. Chromosome abnormality chip with 180 000 probes was used to detect small deletion, small amplification and loss of heterozygosity. RESULTS: By PCR, nine of 103 infertile patients were found to have sequence-tagged site microdeletions. Microdeletions were not observed in control samples. The deletions detected by PCR were present in six azoospermic men (6/44, 13.6%) and in three oligoasthenoteratozoospermic (OATS) men (3/59, 5%). The overall frequency of microdeletions in infertile men was 8.7% (9/103). Chromosome abnormality chip detection 500+ detected more amplification or deletion in 51 infertile patients and the overall frequency of microdeletions in infertile men was 49.5% (51/103). CONCLUSION: Chromosome abnormality chip detection system provides a sensitive, economic and high-throughput method for detecting the deletion or amplification of genomic DNA sequences of infertile patients. Not only can it identify Yq deletions, but it can also find other chromosome abnormalities and facilitate the understanding of male infertility.

OBJETIVO: Analizar la aplicación de la tecnología de los microarreglos en el diagnóstico de la infertilidad masculina. MÉTODOS: Dieciséis loci, incluyendo una región determinante del sexo en el cromosoma Y, fueron investigados mediante reacción en cadena de la polimerasa (RCP) en pacientes hombres con problemas de infertilidad. Un biochip de la anormalidad cromosómica, con 180000 sondas, fue utilizado a fin de detectar pequeñas delecciones, pequeñas amplificaciones y pérdidas de heterocigosidad. RESULTADOS: Por medio de la RCP, se halló que nueve de 103 pacientes con infertilidad presentaban microdelecciones de sitios de secuencia marcada. Las microdelecciones no fueron observadas en las muestras de control. Las delecciones detectadas mediante RCP, estuvieron presentes en seis hombres azoospérmicos (6/44, 13.6%) y en tres hombres con oligoastenoteratozoospermia (OAT) (3/59, 5%). La frecuencia general de las microdelecciones en los hombres infértiles fue 8.7% (9/103). La detección con biochip de la anormalidad cromosómica de 500+ detectó más amplificación y delección en 51 pacientes, y la frecuencia general de microdelecciones en los hombres infértiles fue 49.5% (51/103). CONCLUSIÓN: El sistema de detección de la anormalidad del cromosoma mediante biochips genéticos representa un método sensible, económico, y de alto rendimiento, para detectar la delección o amplificación de las secuencias genómicas de ADN de pacientes infértiles. Este método puede no sólo identificar las delecciones Yq, sino también hallar otras anormalidades cromosómicas, facilitando así la comprensión de la infertilidad en los hombres.

Genomic characterization of some Iranian children with idiopathic mental retardation using array comparative genomic hybridization.

BACKGROUND: Mental retardation (MR) has a prevalence of 1‑3% and genetic causes are present in more than 50% of patients. Chromosomal abnormalities are one of the most common genetic causes of MR and are responsible for 4‑28% of mental retardation. However, the smallest loss or gain of material visible by standard cytogenetic is about 4 Mb and for smaller abnormalities, molecular cytogenetic techniques such as array comparative genomic hybridization (array CGH) should be used. It has been shown that 15‑25% of idiopathic MR (IMR) has submicroscopic rearrangements detectable by array CGH. In this project, the genomic abnormalities were investigated in 32 MR patients using this technique. MATERIALS AND METHODS: Patients with IMR with dysmorphism were investigated in this study. Karyotype analysis, fragile X and metabolic tests were first carried out on the patients. The copy number variation was then assessed in a total of 32 patients with normal results for the mentioned tests using whole genome oligo array CGH. Multiple ligation probe amplification was carried out as a confirmation test. RESULTS: In total, 19% of the patients showed genomic abnormalities. This is reduced to 12.5% once the two patients with abnormal karyotypes (upon re‑evaluation) are removed. CONCLUSION: The array CGH technique increased the detection rate of genomic imbalances in our patients by 12.5%. It is an accurate and reliable method for the determination of genomic imbalances in patients with IMR and dysmorphism.

Congenital heart diseases caused by chromosome abnormality / 国际儿科学杂志

Chromosome abnormality has recently been recognized as an important cause of congenital heart diseases(CHD).The tiny fragment deformity of the chromosome may lead to many abnormal genes expression.Recent studies have disclosed that CHD is a part of syndrome attributed to chromosome abnormality.This article reviews chromosome abnormality caused by trisomy chromosome,chromosome deletions,Tuner syndrome and Kleinfelte's syndrome as well as incidence,type,mechanism and prognosis of its complicated CHD.

Higroma quístico y translucencia nucal aumentada como marcadores de anomalías cromosómicas

Objetivos: Determinar la importancia del espacio retronucal en fetos entre las 11 y 13+6 semanas, identificando sus características, la asociación con anomalías cromosómicas y las posibles diferencias entre higroma quístico y translucencia nucal aumentada. Diseño: Estudio transversal prospectivo. Institución: Instituto Latinoamericano de salud Reproductiva, Lima, Perú. Participantes: Gestantes y sus fetos con diagnóstico citogenético prenatal. Intervenciones: Entre el año 2007 y junio 2012, se revisó 266 casos con diagnóstico citogenético prenatal, que correspondieron a 230 amniocentesis realizadas después de las 14 semanas y 36 biopsias de vellosidades coriales (BVC), entre las 11 a 13 semanas. Principales medidas de resultados: Marcadores ecográficos prenatales. Resultados: Se detectó 106 casos de anomalías cromosómicas (39,9%). El higroma quístico (HQ) fue el marcador que con más frecuencia, en relación al aumento de la translucencia de la nuca (TN) (30,8% versus 11,3%), se asoció a anomalías cromosómicas (68,3% versus 31%), correspondiendo al HQ una sensibilidad (S) de 45%, valor predictivo positivo (VPP) de 62%, ratio de probabilidad+ (LR+) de 2,4, y para la TN aumentada S 11%, VPP 40%, LR+ 1. El HQ se asoció en 35,7% a monosomía X, la TN aumentada a trisomías. Conclusiones: El HQ fue el marcador de anomalías cromosómicas más frecuente encontrado entre las 11 y 13+6 semanas y tuvo mayor valor predictivo que la TN aumentada. Ambas serían dos entidades distintas, siendo necesaria su diferenciación.

Objectives: To determine the importance of nuchal translucence in fetuses 11 to 13 +6 weeks, identifying characteristics, association with chromosomal anomalies and differences between cystic hygroma and increased nuchal translucency. Design: Prospective cross-sectional study. Setting: Instituto Latinoamericano de Salud Reproductiva, Lima, Peru. Participants: Pregnant women and their fetuses with prenatal cytogenetic diagnosis. Interventions: Between 2007 and June 2012, 266 cases with prenatal cytogenetic diagnosis had 230 amniocentesis after 14 gestational weeks and 36 chorionic villi biopsy (CVS) between 11-13 gestational weeks. Main outcome measures: Prenatal ultrasound markers. Results: One hundred and six cases of chromosomal abnormalities (39.9%) were found. Cystic hygroma (CH) was more often found than nuchal translucency (NT) (30.8% versus 11.3%) associated with chromosomal abnormalities (68.3% versus 31%), corresponding to HQ sensitivity (S) 45%, positive predictive value (PPV) 62%, likehood ratio+ (LR+) 2.4, and for increased TN S 11%, PPV 40%, LR+ 1. CH was associated in 35.7% to monosomy X, and NT to trisomy. Conclusions: CH was the most common chromosomal abnormalities marker found between 11 and 13 +6 weeks and had greater predictive value than increased NT. Each would represent separate entities requiring differentiation.

Caracterización citogenético-molecular de enfermedades genéticas en el Hospital Base de Puerto Montt / Cytogenetic and molecular profile of genetic diseases in Puerto Montt main hospital

Background: Chromosome aberrations (CA) are the main etiology of múltiple congenital malformations, recurrent abortions and intellectual disability (ID) specifically of modérate and severe degree. They accountfor 0.3 to 1 percent of newborns (NB) and 6 of 10,000 NB have chromosome imbalances with submicroscopic deletions or duplications smaller than 10 MB that are overlooked by conventional cytogenetic studies. Aim: To report the results of cytogenetic and molecular studies performed in patients with a congenital malformation disease or ID with or without dysmorphic features, attended in a regional hospital. Patients and Methods: One hundred and eighty patients, 27 with a clinical diagnosis ofDown syndrome, derivedfor the sus-picion of a genetic disease, were studied. A karyogram was performed in all ofthem and in 30 cases additional molecular studies, such as fluorescence in situ hybridization (FISH) orpolymerase chain reaction (PCR) were carried out. Results: Amongthe 153 patients without Down syndrome, 20 (13 percent) had a genetic abnormality responsible for the altered phenotype. Sixteen had a chromosome aberration (structural and numerical aberrations in 75 and 25 percent respectively) andfour had genetic molecular alterations. Additional studies were performed to confirm or better characterize the chromosome aberration in 13 ofthe 30 patients in whom these were requested. Conclusions: Chromosome and specific genetic molecular studies in selected cases help to characterize patients with genetic diseases. The collaboration between academic and health care facilities is crucial.