Genetic analysis of three children with disorders of sex development caused by structural rearrangements of Y chromosome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of three children with disorders of sex development (DSD) in association with rare Y chromosome rearrangements.@*METHODS@#The three children, who all featured short stature and DSD, were subjected to G banding chromosomal karyotyping, multiplex PCR for Y chromosomal microdeletion, sequencing of the whole SRY gene, SNP-array analysis for genomic copy number variations, and fluorescence in situ hybridization (FISH).@*RESULTS@#The combined analysis revealed chromosomal abnormalities in all of the three children, including 46,X,t(X;Y)(p22.3;q11.2) in case 1, mos 45,X,der(7)pus dic(Y:7)(p11.3p22)del(7)(p21.2p21.3) del(7)(p12.3p14.3) [56]/45,X [44] in case 2, and mos 45,X [50]/46,X,idic(Y)(q11.22) [42]/47,X,idem×2 [4]/47,XYY [2] in case 3.@*CONCLUSION@#Combined use of genetic techniques can delineate complex rearrangements involving Y chromosome in patients featuring short stature and DSD. Above findings have enabled molecular diagnosis and genetic counseling for the patients.

High frequency of Y chromosome microdeletions in male infertility patients with 45,X/46, XY mosaicism

The mosaic 45,X/46,XY karyotype is a common sex chromosomal abnormality in infertile men. Males with this mosaic karyotype can benefit from assisted reproductive therapies, but the transmitted abnormalities contain 45,X aneuploidy as well as Y chromosome microdeletions. The aim of this study was to investigate the clinical and genetic characteristics of infertile men diagnosed with 45,X/46,XY mosaicism in China. Of the 734 infertile men found to carry chromosomal abnormalities, 14 patients were carriers of 45,X/46,XY mosaicism or its variants, giving a prevalence of 0.27% (14/5269) and accounting for 1.91% (14/734) of patients with a chromosomal abnormality. There were ten cases (71.43%, 10/14) of 45,X mosaicism exhibiting AZF microdeletions. Case 1 and Case 4 had AZFc deletions, and the other eight cases had AZFb+c deletions. A high frequency of Y chromosome microdeletions were detected in male patients with 45,X/46,XY mosaicism. Preimplantation genetic diagnosis should be offered to men having intracytoplasmic sperm injection for hypospermatogenesis caused by 45,X/46,XY mosaicism, to avoid the risk of transfering AZF microdeletions in addition to X monosomy in male offspring.

Incidence of Y-chromosome microdeletions in children whose fathers underwent vasectomy reversal or in vitro fertilization with epididymal sperm aspiration: a case-control study / Incidência de microdeleções do cromossomo Y em filhos de pais que passaram por reversão de vasectomia ou fertilização in vitro com aspiração do epidídimo: um estudo caso-controle

ABSTRACT Objective To evaluate the incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with sperm retrieval by epididymal aspiration (percutaneous epididymal sperm aspiration). Methods A case-control study comprising male children of couples in which the man had been previously vasectomized and chose vasectomy reversal (n=31) or in vitro fertilization with sperm retrieval by percutaneous epididymal sperm aspiration (n=30) to conceive new children, and a Control Group of male children of fertile men who had programmed vasectomies (n=60). Y-chromosome microdeletions research was performed by polymerase chain reaction on fathers and children, evaluating 20 regions of the chromosome. Results The results showed no Y-chromosome microdeletions in any of the studied subjects. The incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with spermatozoa recovered by percutaneous epididymal sperm aspiration did not differ between the groups, and there was no difference between control subjects born from natural pregnancies or population incidence in fertile men. Conclusion We found no association considering microdeletions in the azoospermia factor region of the Y chromosome and assisted reproduction. We also found no correlation between these Y-chromosome microdeletions and vasectomies, which suggests that the assisted reproduction techniques do not increase the incidence of Y-chromosome microdeletions.

RESUMO Objetivo Avaliar a incidência de microdeleções do cromossomo Y em indivíduos nascidos de pais vasectomizados submetidos à reversão de vasectomia ou fertilização in vitro com recuperação de espermatozoides por aspiração do epidídimo (aspiração percutânea de espermatozoides do epidídimo). Métodos Estudo caso-controle que compreende crianças do sexo masculino de casais em que o homem havia sido previamente vasectomizado e escolheu reversão da vasectomia (n=31) ou fertilização in vitro com recuperação espermática por aspiração percutânea de espermatozoides do epidídimo (n=30) para obtenção de novos filhos, e um Grupo Controle de crianças do sexo masculino de homens férteis com vasectomia programada (n=60). A pesquisa de microdeleções do cromossomo Y foi realizada por reação em cadeia da polimerase nos pais e filhos, avaliando 20 regiões do cromossomo. Resultados O resultado não revelou microdeleções do cromossomo Y em qualquer indivíduo estudado. A incidência de microdeleções do cromossomo Y em indivíduos nascidos de pais vasectomizados que sofreram reversão de vasectomia ou fertilização in vitro com espermatozoides recuperados pela aspiração percutânea de espermatozoides do epidídimo não diferiu entre os grupos, e não houve nenhuma diferença entre indivíduos controle nascidos de gestações naturais ou incidência populacional em homens férteis. Conclusão Não foi encontrada nenhuma associação considerando microdeleções da região do fator de azoospermia no cromossomo Y e reprodução assistida. Não houve correlação entre microdeleções do cromossomo Y e vasectomia, o que sugere que as técnicas de reprodução assistida não aumentam a incidência de microdeleções do cromossomo Y.

Doble aneuploidía (trisomía X, trisomía 18) en una recién nacida con fenotipo de trisomía 18 / Double aneuploidy (trisomy x, trisomy 18) in a newborn with trisomy 18 phenotype

Se presenta el caso de una recién nacida con una doble trisomía, con complemento cromosómico 48,XXX,+18, con fenotipo de síndrome de Edwards (trisomía 18). Las características clínicas fueron restricción del crecimiento intrauterino, facies dismórfca, mano con sobreposición de dedos, comunicación interventricular, estenosis pulmonar y pie equinovaro izquierdo. Se realiza una revisión de la bibliografía y discusión de los casos previamente comunicados.

We report the case of a newborn girl with a double trisomy, with a chromosome complement 48,XXX,+18, with Edwards syndrome phenotype (trisomy 18). The clinical feature included intrauterine growth retardation, dysmorphic facies, hand with overlapping fngers, ventricular septal defect, pulmonary stenosis and left clubfoot. A review of the literature and discussion of previously reported cases is made.

Mosaic double aneuploidy: Down syndrome and XYY.

Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5‑year‑old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management.

Triple X Egyptian woman and a Down's syndrome offspring.

The 47, XXX karyotype (triple X) has a frequency of 1 in 1000 female newborns. However, this karyotype is not usually suspected at birth or childhood. Female patients with a sex chromosome abnormality may be fertile. In patients with a 47, XXX cell line there appears to be an increased risk of a cytogenetically abnormal child but the extent of this risk cannot yet be determined; it is probably lower in the non-mosaic 47, XXX patient than the mosaic 46, XX/47, XXX one. We describe a new rare case of triple X woman and a Down's syndrome offspring. The patient is 26 years of age. She is a housewife, her height is 160 cm and weight is 68 kg and her physical features and mentality are normal. She has had one pregnancy at the age of 25 years resulted in a girl with Down's syndrome. The child had 47 chromosomes with trisomy 21 (47, XX, +21) Figure 1. The patient also has 47 chromosomes with a triple X karyotype (47, XX, +X) Figure 2. The patient's husband (27 years old) is physically and mentally normal. He has 46 chromosomes with a normal XY karyotype (46, XY). There are neither Consanguinity between her parent's nor she and her husband.