Clinical and genetic analysis of 6 families with Helsmoortel-Van der Aa syndrome
10.3760/cma.j.cn101070-20231226-00450
- VernacularTitle:Helsmoortel-Van der Aa综合征6家系临床及遗传学特点分析
- Author:
Haihua YANG
1
;
Huifang YAN
;
Junyu WANG
;
Yu ZHANG
;
Jingmin WANG
Author Information
1. 北京大学第一医院儿科，北京 100034
- Keywords:
Helsmoortel-Van der Aa syndrome;
ADNP;
Developmental delay
- From:
Chinese Journal of Applied Clinical Pediatrics
2024;39(7):537-539
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze and determine the clinical and genetic characteristics of children with Helsmoortel-Van der Aa syndrome(HVDAS).Methods:Clinical data of 6 children with HVDAS treated at the First Hospital of Peking University from November 2018 to October 2022 and their family members were collected and analyzed retrospectively.Whole exome sequencing was performed on children and their family members to identify the genetic variants.Genotype and phenotype correlation was analyzed.Results:(1) Clinical analysis results: among the 6 children, there were 5 boys and 1 girl, and their age at diagnosis ranged from 11 months and 17 days to 12 years and 9 months.Six patients all presented with developmental delays/intellectual disabilities; (2) Genetic analysis results: 6 de novo ADNP variants were discovered in 6 children, including 1 initial codon deletion variant c. 1_2del, 2 nonsense variants c. 1175dup, p.(Tyr392*) and c. 2213C>G, p.(Ser738*), and 3 frameshift variants c. 2632dup, p.(Ser878Lysfs*3), c.1695_1696insATGGTATGTATGTATGTATG, p.(Val566Metfs*8) and c. 2120_2123del, p.(Asn707Serfs*8).All variants were classified as pathogenic variants by the American College of Medical Genetics and Genomics.Except the c. 2213C>G, p.(Ser738*), the other 5 variants are all novel variants that have not been reported before. Conclusions:All of the 6 cases of HVDAS showed typical clinical manifestations, and expanded the phenotype spectrum of microcephaly and tall stature.Six de novo mutations were discovered, expanding the ADNP mutation spectrum and providing accurate genetic counseling and prenatal genetic diagnosis of the disease.
