Clinical and genetic characteristic in patients with disorders of sex development caused by Y chromosome copy number variant.
10.3760/cma.j.cn112140-20221115-00965
- VernacularTitle:Y染色体拷贝数变异致性发育异常的临床和遗传学特点
- Author:
Jun Ke XIA
1
;
Feng Yan TIAN
2
;
Ya Qin HOU
1
;
Yong Jiang ZHAO
1
;
Xiang Dong KONG
1
Author Information
1. Prenatal and Genetic Diagnosis Center, Department of Gynaecology and Obstetrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
2. Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
- Publication Type:Journal Article
- MeSH:
Humans;
Female;
DNA Copy Number Variations;
In Situ Hybridization, Fluorescence;
Retrospective Studies;
Chromosomes, Human, Y;
Turner Syndrome
- From:
Chinese Journal of Pediatrics
2023;61(5):459-463
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the clinical phenotype and genetic characteristics of disorders of sex development (DSD) caused by Y chromosome copy number variant (CNV). Methods: A retrospective analysis was performed on 3 patients diagnosed with DSD caused by Y chromosome CNV admitted to the First Affiliated Hospital of Zhengzhou University from January, 2018 to September, 2022. Clinical data were collected. Clinical study and genetic test were performed by karyotyping, whole exome sequencing (WES), low coverage whole genome copy number variant sequencing (CNV-seq), fluorescence in situ hybridization (FISH) and gonadal biopsy. Results: The 3 children, aged 12, 9, 9 years, the social gender were all female, presented with short stature, gonadal dysplasia and normal female external genital. No other phenotypic abnormality was found except for case 1 with scoliosis. The karyotype of all cases were identified as 46, XY. No pathogenic vraiants were found by WES. CNV-seq determined that case 1 was 47, XYY,+Y(2.12) and case 2 was 46, XY,+Y(1.6). FISH concluded that the long arm of Y chromosome was broken and recombined near Yq11.2, and then produced a pseudodicentric chromosome idic(Y). The karyotype was reinterpreted as mos 47, X, idic(Y)(q11.23)×2(10)/46, X, idic(Y)(q11.23)(50) in case 1. The karyotype was redefined as 45, XO(6)/46, X, idic(Y)(q11.22)(23)/46, X, del(Y)(q11.22)(1) in case 2. 46, XY, -Y(mos) was found by CNV-seq in case 3, and the karyotype of 45, XO/46, XY was speculated. Conclusions: The clinical manifestations of children with DSD caused by Y chromosome CNV are short stature and gonadal dysgenesis. If there is an increase of Y chromosome CNV detected by CNV-seq, FISH is recommended to classify the structural variation of Y chromosome.
