Microdeletions and vertical transmission of the Y-chromosome azoospermia factor region / 亚洲男科学杂志(英文版)

Spermatogenesis is regulated by several Y chromosome-specific genes located in a specific region of the long arm of the Y chromosome, the azoospermia factor region (AZF). AZF microdeletions are the main structural chromosomal abnormalities that cause male infertility. Assisted reproductive technology (ART) has been used to overcome natural fertilization barriers, allowing infertile couples to have children. However, these techniques increase the risk of vertical transmission of genetic defects. Despite widespread awareness of AZF microdeletions, the occurrence of de novo deletions and overexpression, as well as the expansion of AZF microdeletion vertical transmission, remains unknown. This review summarizes the mechanism of AZF microdeletion and the function of the candidate genes in the AZF region and their corresponding clinical phenotypes. Moreover, vertical transmission cases of AZF microdeletions, the impact of vertical inheritance on male fertility, and the prospective direction of research in this field are also outlined.

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.

Application of prenatal bacterial artificial chromosome-on-beads identification/isolation technology in the diagnosis of chromosomal aneuploidy and microdeletion/microduplication syndrome / 中华检验医学杂志

Objective:To explore the indication of bacterial artificial chromosome-on-beads identification/separation technology in prenatal diagnosis and its application value.Methods:The inclusion criteria were as follows: age ≥35 years, high risk/critical risk of serological prenatal screening, high risk of non-invasive gene testing (NIPT), abnormal ultrasonic indexes or adverse pregnancy history. From April 2016 to December 2020, 3579 amniotic fluid samples collected from pregnant women with singletons were detected by bacterial artificial chromosome-on-beads identification/separation technique (BoBs) and G-banding karyotype analysis simultaneously. The aneuploid abnormality/microdeletion/microdeletion samples detected by karyotype analysis or BoBs were verified by fluorescence in situ hybridization (FISH)/SNP array as needed.Results:(1) The percentage of samples with indications of advanced maternal age, high risk of NIPT and high risk of serological screening was 89.44%(3 201/3 579), the detection rate of aneuploidy was 96.19%(202/210), and the detection rate of microdeletion/microduplication was 87.5%(28/32),the total abnormal detection rate was 95.04% (230/242). The samples with abnormal ultrasonic indexes, adverse pregnancy history and critical risk indications of serological screening in the second trimester accounted for 10.66%, and the abnormality of aneuploidy and micro-duplication/micro-deletion was 4.96%. (2) 198 common chromosome aneuploidies (13/18/21/X/Y) were detected by BoBs, and 12 cases with chimeras ≥20% were found, which were consistent with karyotype results. Two copies of 21-trisomy, three copies of X/Y, seven copies of 2, 7, 8, 9, 10, 20, mar karyotype chimerism, eight copies of arm inversion and five copies of translocation outside the detection range of probes were detected by karyotype analysis. The sensitivity, specificity and false negative rate of BoBs detection for five aneuploidies were 94.6%(210/222), 100% and 5.4%(12/222), respectively. BoBs and karyotype analysis detected 32 and 9 cases of microdeletions/microduplications respectively. Compared with single karyotype analysis, the combined application of G-banding karyotype analysis and BoBs can detect an additional 9.4% (23/244)positive samples.Conclusion:The samples with elder age, high risk of NIPT, and high risk of serological screening are more suitable as indications for the application of BoBs in prenatal diagnosis.

Genetic analysis of a family with 6q22 microdeletion and 10p15.3p13 microduplication in two consecutive pregnancies / 中华检验医学杂志

Objective:Cytogenetic and molecular genetic analysis was performed on two consecutive antenatal abnormal fetuses and their parents in a family to clarify the copy number variation(CNV) and its mechanism.Methods:The karyotypes of two fetuses and their parents were analyzed by conventional karyotyping techniques, and CNVs of two fetuses and their mother were analyzed by low-coverage whole-genome copy number variation sequencing (CNV-seq) techniques.Results:The amniotic fluid karyotype results of fetus 1 and 2 were 46, XN, der(4)t(4;10)(q35;p13). The mother′s peripheral blood karyotype result was 46, XX, t(4;10)(q35;p13), and the father′s karyotype was normal. The CNV-seq results of fetus 1 and 2 were seq[hg19]6q22.31(122740000-125440000)X1; 10p15.3p13(120000-17260000)X3, suggesting that there was a heterozygous deletion of about 2 700 000 bp in fetal 6q22.31 and a duplication of about 17 140 000 bp in fetal 10p15.3p13. The CNV-seq result of their mother was seq[hg19]6q22.31(122740000-125440000)X1, suggesting that there was a heterozygous deletion of about 2 700 000 bp in 6q22.31. The pregnant woman and her family chose to terminate the pregnancy after genetic consulting.Conclusion:The combined application of karyotyping and CNV-Seq is significantly beneficial to detecting microdeletions or microduplications of fetal chromosomes and effectively preventing the birth of defective children.

Clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children.@*METHODS@#The medical data of 200 children with epilepsy who underwent a genetic analysis of epilepsy by the whole exon sequencing technology were collected retrospectively, of whom 9 children with epilepsy had 16p11.2 microdeletion. The clinical phenotype and genetic features of the 9 children with 16p11.2 microdeletion were analyzed.@*RESULTS@#The detection rate of 16p11.2 microdeletion was 4.5% (9/200). The 9 children with 16p11.2 microdeletion were 3-10 months old. They experienced focal motor seizures with consciousness disturbance, and some of the seizures developed into generalized tonic-clonic seizures. The interictal electroencephalogram showed focal or multifocal epileptiform discharge, and all 9 children responded well to antiepileptic drugs. The 9 children had a 16p11.2 deletion fragment size of 398-906 kb, and the number of deleted genes was 23-33 which were all pathogenic mutations. The mutation was of maternal origin in 2 children, of paternal origin in 1 child, and de novo in the other children.@*CONCLUSIONS@#16p11.2 microdeletion can be detected in some children with epilepsy. Most of the 16p11.2 microdeletion is de novo mutation and large gene fragment deletion. The onset of 16p11.2 microdeletion-related epilepsy in children is mostly within 1 year of life, and the epilepsy is drug-responsive.

Aspectos genéticos moleculares del síndrome de trombocitopenia con ausencia de radios / Molecular genetic aspects of the thrombocytopenia syndrome with absent radii

Introducción: La trombocitopenia con ausencia de radios es un síndrome genético poco frecuente. Se caracteriza por la ausencia bilateral de radios con presencia de ambos pulgares y trombocitopenia. Pueden estar presentes, además, malformaciones en miembros inferiores, cardiovasculares, gastrointestinales, neurológicas y vasculares. Objetivo: Analizar los aspectos genéticos moleculares más recientes del síndrome de trombocitopenia. Métodos: Se realizó una revisión de la literatura en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico, de artículos publicados en los últimos 10 años. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: El patrón de herencia de la enfermedad es autosómico recesivo, un heterocigótico compuesto por un alelo nulo del gen RBM8A, localizado en el locus 1q21.1 y la presencia de un polimorfismo de simple nucleótido en regiones no codificantes en el otro alelo. Este gen codifica la proteína Y14, la cual es uno de los cuatro componentes del complejo de unión de exones, complejo multiproteico que se une al ARNm y que, una vez finalizado el empalme, interviene en la eficiencia de la traducción y la degradación del ARNm que presenten codones de terminación prematura. Conclusiones: La trombocitopenia es la primera enfermedad en el humano en la que se describe un defecto en una subunidad del complejo de unión de exones. A pesar del avance en los últimos años en el conocimiento de las bases moleculares de la enfermedad, aún son necesarias nuevas investigaciones para explicar la relación entre el gen RBM8 y las manifestaciones esqueléticas(AU)

Introduction: Thrombocytopenia with absent radii is a rare genetic syndrome, characterized by bilateral absence of the radii with the presence of both thumbs and thrombocytopenia. In addition, malformations may be present, involving the lower limbs, as well as the cardiovascular, gastrointestinal, neurological, and vascular systems. Objective: To analyze the most recent molecular genetic aspects of thrombocytopenia syndrome. Methods: A review of the literature in English and in Spanish was carried out, in the PubMed website and using the search engine of Google Scholar, for articles published in the last ten years. We performed analysis and summary of the reviewed bibliography. Information analysis and synthesis: The disease has an autosomal recessive inheritance pattern, a heterozygote composed of a null allele of the RBM8A gene, located at the 1q21.1 locus and the presence of a single nucleotide polymorphism in non-coding regions in the other allele. This gene encodes the Y14 protein, which is one of the four components of the exon-binding complex, a multiprotein complex that binds to mRNA and that, once splicing is complete, intervenes in the efficiency of translation and degradation of mRNA that have premature termination condons. Conclusions: Thrombocytopenia is the first disease in humans in which a defect in a subunit of the exon binding complex was described. Despite the advance in recent years in understanding the molecular basis of the disease, new research is still necessary to explain the relationship between the RBM8 gene and skeletal manifestations(AU)

Algoritmo para el diagnóstico de pacientes con trastornos del neurodesarrollo y sospecha de un síndrome genético / Algorithm for the diagnosis of patients with neurodevelopmental disorders and suspicion of a genetic syndrome

El amplio espectro de aberraciones cromosómicas observable en los trastornos del neurodesarrollo no siempre puede ser caracterizado por análisis cromosómico. El objetivo del trabajo fue determinar la etiología genética de estos trastornos en pacientes con afecciones neurológicas congénitas y sospecha clínica de un síndrome genético, aplicando un algoritmo de estudio clínico-molecular. En 71 de 111 niños analizados, se hallaron aberraciones submicroscópicas asociadas a síndromes de microdeleción-microduplicación: DiGeorge (22 casos), Prader-Willi (26 casos), Angelman (2 casos), Williams-Beuren (17 casos), Smith-Magenis (1 caso), Miller-Dieker (1 caso) y síndrome cri du chat (1 caso). Adicionalmente, se detectó una inserción desbalanceada de novo de la región 17p12p11.2, en el punto 5p13.1, en un niño de tres años. La utilización del método clínico unido a técnicas moleculares, como hibridación fluorescente in situ, ha permitido, en la mayoría de los casos, el diagnóstico certero de pacientes y/o familias con trastornos del neurodesarrollo.

The wide range of chromosome aberrations seen in neurodevelopmental disorders may not always be characterized by means of a chromosome analysis. The objective of this study was to determine the genetic etiology of these disorders in patients with congenital neurological conditions and clinical suspicion of a genetic disorder using a clinical and molecular testing algorithm. Among 111 studied children, 71 showed submicroscopic chromosome aberrations associated with microdeletion/microduplication syndromes: DiGeorge (22 cases), Prader-Willi (26 cases), Angelman (2 cases), Williams-Beuren (17 cases), Smith-Magenis (1 case), Miller-Dieker (1 case), and cri du chat syndrome (1 case). Additionally, a de novo trisomy 17p12p11.2 due to an unbalanced insertion into 5p13.1 was identified in a 3-year-old child. In most cases, the use of a clinical method together with molecular techniques, such as fluorescence in situ hybridization, has allowed to make an accurate diagnosis in patients and/or families with neurodevelopmental disorders.

Research progress on mechanism of TBX1 gene affecting phenotype of 22q11.2 microdeletion syndrome / 医学研究生学报

22q11.2 microdeletion syndrome is a genetic syndrome caused by the deletion of 22q11.21-q11.23 in the proximal long arm microfragment of chromosome 22 for human. TBX1 belongs to the T-box family and is located in 22q11.2 of chromosome. Studies have shown that haploinsufficiency of TBX1 is the main cause of 22q11.2 microdeletion syndrome, which is of great significance for the appearance of its phenotype. Therefore, this paper reviews the research progress of TBX1 in the mechanism of cardiac disease, pulmonary artery phenotype, thymus development, pharyngeal and palatal development, lymphatic formation, and low proliferation of parathyroid tumors.

Research progress on mechanism of TBX1 gene affecting phenotype of 22q11.2 microdeletion syndrome / 医学研究生学报

22q11.2 microdeletion syndrome is a genetic syndrome caused by the deletion of 22q11.21-q11.23 in the proximal long arm microfragment of chromosome 22 for human. TBX1 belongs to the T-box family and is located in 22q11.2 of chromosome. Studies have shown that haploinsufficiency of TBX1 is the main cause of 22q11.2 microdeletion syndrome, which is of great significance for the appearance of its phenotype. Therefore, this paper reviews the research progress of TBX1 in the mechanism of cardiac disease, pulmonary artery phenotype, thymus development, pharyngeal and palatal development, lymphatic formation, and low proliferation of parathyroid tumors.

Y chromosome microdeletion screening using a new molecular diagnostic method in 1030 Japanese males with infertility / 亚洲男科学杂志(英文版)

The azoospermia factor (AZF) region is important for spermatogenesis, and deletions within these regions are a common cause of oligozoospermia and azoospermia. Although several studies have reported this cause, the present research, to the best of our knowledge, is the first large-scale study assessing this factor in Japan. In this study, 1030 male patients with infertility who were examined for Y chromosome microdeletion using the polymerase chain reaction-reverse sequence-specific oligonucleotide (PCR-rSSO) method, a newly developed method for Y chromosome microdeletion screening, were included. The study enrolled 250 patients with severe oligospermia and 717 patients with azoospermia. Among the 1030 patients, 4, 4, 10, and 52 had AZFa, AZFb, AZFb+c, and AZFc deletions, respectively. The sperm recovery rate (SRR) of microdissection testicular sperm extraction in patients with AZFc deletions was significantly higher than that in those without AZF deletions (60.0% vs 28.7%, P = 0.04). In patients with gr/gr deletion, SRR was 18.7%, which was lower than that in those without gr/gr deletion, but was not statistically significant. In conclusion, our study showed that the frequency of Y chromosome microdeletion in male patients in Japan was similar to that reported in patients from other countries, and SRR was higher in patients with AZFc deletion.

Chinese Siblings with Prader-Willi Syndrome Inherited from Their Paternal Grandmother

Background: Prader-Willi syndrome (PWS) is a complex neurobehavioral disorder causedby failure of expression of paternally inherited genes in the PWS region of chromosome 15.Case characteristics: Two siblings who both met the inclusion criteria for clinical diagnosisof PWS during neonatal period. Outcome: Molecular genetic analysis demonstrated a 417-kb microdeletion within the 15q11.2 region inherited from siblings’ paternal grandmother,involving key genes of PWS, except for UBE3A, which may explain why their father andpaternal grandmother had a normal phenotype. Conclusion: The findings may be helpfulfor better understanding of the underlying mechanism of this rare imprinting defect

Familial Y chromosome microdeletion with pericentric inversion of chromosome 19 / 中华男科学杂志

Objective@#To investigate the familial cytomolecular genetics of an infertile male.@*METHODS@#We analyzed the clinical phenotypes and karyotypes of three males from the family of an infertile man, detected the sequence-tagged sites (STS) in the AZF deletions of the Y chromosome by multiplex polymerase chain reaction (PCR), and identified the target genes by multiplex ligation-dependent probe amplification (MLPA).@*RESULTS@#The karyotypes of the proband and his brother were 46, XY, inv (19) (p13.3q13.1) and that of his father was 46, XY. The three males were all carriers of AZFc deletion of the Y chromosome, and all found with the same reduction of the gene copy number in the AZFb and AZFc regions.@*CONCLUSIONS@#Combined use of karyotype analysis, Y chromosome STS PCR, and MLPA revealed the genetic causes of the male infertile family.

Preliminary study on the clinical value of noninvasive prenatal testing of fetal chromosomal copy number variations / 中国实用妇科与产科杂志

OBJECTIVE: To explore the clinical value of non-invasive prenatal testing(NIPT)for screening fetal chromosomal copy number variations(CNVs) and microdeletion/microduplication syndromes(MDs).METHODS: Retrospective analysis was made in the 10 005 women who received NIPT during the first trimester(15-20+ 6 weeks)from January,2012 to July,2017,at First People's Hospital of Yunnan Province,Department of Genetic Diagnosis Center.Among them 32 pregnant women were indicated fetal CNVs,25 of 32 pregnant women selected interventional prenatal diagnosis.Statistical analysis was made on the amniotic fluid/cord blood chromosome G band karyotype and high-throughput sequencing(NGS)genome copy number analysis was made,and relevant CNVs were searched and analyzed in the corresponding database;the consistency of CNVs found in NIPT with interventional prenatal diagnosis was statistically analyzed.RESULTS: During the second trimester(15-20+ 6 weeks),in the 10 005 pregnant women who received NIPT testing 32 cases were shown to have high risks of fetal CNVs,and the screening positive rate was 0.32%(32/10 005).In 25 high risk pregnant women who accepted invasive prenatal diagnosis via informed choice,14 women wereconfirmed as fetal CNVs,the positive predictive value(PPV)of NIPT being 56%(14/25),including 9 cases of microdeletion and 5 cases of microduplication.The sizes were between 587.75 kb and 36.05 Mb.The size and the start and end positions of CNVs found by NIPT were similar to those of fetal DNA samples detected by NGS.Among 14 cases of fetal CNVs,11 cases were identified as MDs,3 cases as unknown clinical significance.In 11 cases of MDs,8 cases were observed fetal chromosome structure abnormalities by karyotype analysis,10 cases were confirmed as de novo abbreviations,and 2 cases as originated from paternal same MD.After genetic counseling,10 pregnant women in 11 cases of MDs chose informed terminations,and one case chose continuing pregnancy.CONCLUSION: As a high-precision screening method,NIPT is expected to be an effective mean to screen for fetal CNVs,which can be used to detect highrisk chromosome microdeletion and microduplication CNVs of larger segments.High risk cases of fetal CNVs found by NIPT require invasive prenatal diagnosis for validation.

Prenatal diagnosis of a case with Branchi-oto-renal syndrome / 中华医学遗传学杂志

Objective@#To carry out prenatal diagnosis for a women with Branchio-oto-renal syndrome by using chromosomal microarray analysis (CMA).@*Methods@#Peripheral blood chromosomal karyotyping and CMA were used to analyze the gravida with an abnormal phenotype. Pathological copy number variants (CNVs) were validated in other members of the family members and her fetus.@*Results@#The gravida and her daughter both had Branchio-oto-renal syndrome and a 8q13.3 microdeletion encompassing the EYA1 gene. The same microdeletion was also found in the fetus. No phenotypic or genotypic anomaly was found with other members of the family.@*Conclusion@#Mutation of the EYA1 gene probably underlies the Branchio-oto-renal syndrome in this family, which is consistent with an autosomal dominant inheritance.

Phenotypic and genetic analysis of a pedigree with 4p16 microduplication and 8p23 microdeletion / 中华医学遗传学杂志

Objective@#To explore the nature and origin of chromosomal copy number variants (CNVs) in a pedigree affected with mental retardation.@*Methods@#Genomic CNVs of the proband were analyzed by next generation sequencing (NGS). Chromosomal karyotypes of the proband and his relatives were analyzed with high-resolution karyotyping and fluorescence in situ hybridization (FISH).@*Results@#Clinical phenotypes of the proband and other patients from the pedigree included mental retardation and mild dysmorphism. The results of NGS revealed that the proband carried a 16.24 Mb microduplication at 4p16.3-15.32 and a 2.2 Mb microdeletion at 8p23.3-23.2. Other patients of the pedigree harbored the same variants, while those without the phenotypes did not harbor the variants. The results of high-resolution karyotyping and FISH revealed that the mother of the proband carried a reciprocal translocation between 4p and 8p, and her karyotype was 46, XX, t(4; 8)(p16; p23). No karyotypic abnormality was detected in his father.@*Conclusion@#The abnormal phenotypes of this pedigree may be attributed to 4p microduplication in conjunct with 8p microdeletion derived from a maternal balanced translocation between 4p and 8p.

1q21.1 microdeletion identified by chromosomal microarray in a newborn with upper airway obstruction

A 1q21.1 microdeletion is an extremely rare chromosomal abnormality that results in phenotypic diversity and incomplete penetrance. Patients with a 1q21.1 microdeletion exhibit neurological-psychiatric problems, microcephaly, epilepsy, facial dysmorphism, cataract, and thrombocytopenia absent radius syndrome. We reported a neonate with confirmed intrauterine growth restriction (IUGR), micrognathia, glossoptosis, upper airway obstruction, facial dysmorphism, and eye abnormality at birth as well as developmental delay at the age of 1 year. These clinical manifestations, except for the IUGR and upper airway obstruction, in the neonate indicated a 1q21.1 microdeletion. Here, we report a rare case of a 1q21.1 microdeletion obtained via paternal inheritance in a newborn with upper airway obstruction caused by glossoptosis and tracheal stenosis.

RELATIONSHIP BETWEEN Y CHROMOSOME MICRODELETION AND SEXUAL HORMONES IN INFERTILE MALE PATIENTS / Шинэ санаа Шинэ нээлт

@#BACKGROUND. In the world, infertility occurs in 10-15% of the total couples and male infertility accounts for 40-50% of the infertile cases. Infertility frequency in Mongolia is 8.7% in 2003 and 11.6% in 2013. According to the Child and Maternity hospital study, 25.6% of infertility is due to men. Microdeletions of the Y chromosome long arm are the most common molecular genetic causes of severe infertility in men. They affect three regions including azoospermia factors (AZFa, AZFb and AZFc), which contain various genes involved in spermatogenesis. OBJECTIVES. The aim of the present study is to investigate the relationship between sexual hormones and AZF microdeletion on Y chromosome in Mongolian infertile men with azoospermia and severe oligozoospermia. MATERIAL AND METHODS. Through a cross sectional study, 50 infertile men were examined for Y chromosome microdeletions from January 2018 to August 2018. We determined hormone level, testis biopsy and microdeletions of the Y chromosome using six loci of 3 regions of the AZF gene were investigated by multiplex polymerase chain reaction. Semen analysis was performed on samples obtained by self-masturbation at the hospital after 2-7 days of sexual abstinence. Reproductive hormone level in serum including total testosterone, follicular stimulating hormone (FSH), and LH is measured at time 8 am to 11 am. If sperm is not recovered, testicular biopsy was performed on the patient. All collected datas were evaluated with Statistical Package for Social Sciences (SPSS, version 22.0). RESULTS. The rate of microdeletion was 4.0% (2 out of 50 patients). The deletion was on AZFa in the first patient, AZFc in the second patient. The patients with Y chromosome microdeletion had azoospermia. AZFa deleted patient has sertoli cell only syndrome in testis biopsy with FSH 58.0 mIU/ml, LH 12.0 mIU/ml, total testosterone 5.0 ng/ml. AZFc deleted patient had FSH 23.85 mIU/ml, LH 13.01 mIU/ml, total testosterone 4.06 ng/ml. Serum FSH and LH levels were significantly higher in Y chromosome deleted group and FSH level was significantly lower in sperm-retrieved group on TESE. СONCLUSION. We determined 2 cases of Y chromosome microdeletion (4.0%) in infertile men. Serum FSH and LH levels were significantly higher in Y chromosome deleted group.

Prenatal ultrasonic manifestations and prognostic analysis of 17q12 microdeletion syndrome / 中华超声影像学杂志

Objective To summarize and analyze the prenatal ultrasonic manifestations of 17q12 microdeletion syndrome ,so as to provide help for prenatal diagnosis . Methods It carried out a retrospective analysis of 21 cases of 17q12 microdeletion syndrome prenatally confirmed by chromosomal microarray analysis(CMA) in the third affiliated hospital of Zhengzhou University from 2015 .01 to 2018 .05 . Prenatal ultrasound findings were collected . A close follow-up was given for the cases . Results Of the 21 fetus ,20 cases were presented with bilateral hyperechogenic kidneys ,and 1 case showed duodenal obstruction . There were 4 cases accompanied with polyhydramnios ,8 cases with mild polyhydramnio ,and 9 cases with normal amniotic fluid index . Parents of 6 fetus underwent chromosomal examination ,of which 2 cases were inherited from the mother and 4 cases had new chromosomal mutations;Seven cases had a family history of diabetes and 3 cases had a family history of kidney disease;Twelve cases performed induced labor ,2 cases lost follow-up and 1 case was unborn . Six cases were born ,of the 6 cases ,1 case associated with mild dysmorphic facial features , and 1 case associated with bilateral renal cysts . Conclusions 17q12 microdeletion syndrome has specific prenatal ultrasound characteristics ,while echogenic kidneys are of great value in the diagnosis of 17q12 microdeletion syndrome prenatally .

An infertile patient with Y chromosome b1/b3 deletion presenting with congenital bilateral absence of the vas deferens with normal spermatogenesis / 대한생식의학회지

We report the case of a 46-year-old Chinese male patient who visited our clinic complaining of infertility. Semen analysis revealed azoospermia, and azoospermia factor c region partial deletion (b1/b3) was detected using Y chromosome microdeletion analysis. Testicular sperm extraction was performed after genetic counseling. The bilateral ductus deferens and a portion of the epididymis were absent, whereas the remaining epididymis was expanded. Motile intratesticular spermatozoa were successfully extracted from the seminiferous tubule. On histopathology, nearly complete spermatogenesis was confirmed in almost every seminiferous tubule. To our knowledge, this is the first case report of b1/b3 deletion with a congenital bilateral absence of the vas deferens and almost normal spermatogenesis.

Microdeleción 16p11. 2: primeros casos reportados en Argentina / 16p11. 2 Microdeletion: first report in Argentina

La microdeleción 16p11.2 se relaciona, habitualmente, con discapacidad intelectual y trastornos del espectro autista. El rango fenotípico incluye un espectro que se extiende desde discapacidad intelectual con o sin autismo, alteraciones del aprendizaje y del lenguaje hasta fenotipos normales. El diagnóstico de la microdeleción se realiza mediante estudios genómicos capaces de identificar variación en número de copias, como la hibridación genómica comparativa en microarreglos, conocida como arrayCGH. Sin embargo, la predicción del fenotipo de un individuo basada únicamente en la localización de dicha deleción sigue siendo un desafío, ya que la existencia de un gran número de variantes en el genoma dificulta la interpretación de posibles efectos funcionales de los genes que contribuyen a dicha región. Se describen dos casos clínicos de pacientes con microdeleción heterocigota en 16p11.2 y se destacan los hallazgos fenotípicos y conductuales que dificultaron la estrategia diagnóstica. También se discuten las implicancias del diagnóstico para el asesoramiento genético familiar.

The 16p11.2 recurrent microdeletion phenotype is characterized by developmental delay, intellectual disability, and/or autism spectrum disorder. This microdeletion is associated with variable clinical outcome, the phenotypical spectrum ranges from intellectual disability and/or multiple congenital anomalies, autism, learning and speech problems, to a normal phenotype. Genomic testing that determines copy number of sequences, such as chromosomal microarray, is used to identify this microdeletion. However, the prediction of the individual phenotype of a patient based only on the location of such deletion remains a challenge, regarding the existence of many genomic variants that might hinder the interpretation of possible functional effects between most of the contributing genes to that region. We describe the clinical findings in two subjects with heterozygous microdeletions at 16p11.2, highlighting the phenotypic and behavioural findings that conditioned the diagnostic strategy. We also discuss the implications of diagnosis, in practical counselling situations.