Clinical and genetic analysis of a patient with Baraitser-Winter syndrome due to variant of ACTG1 gene
10.3760/cma.j.cn511374-20230411-00201
- VernacularTitle:ACTG1基因变异致Baraitser-Winter综合征1例患儿的临床及遗传学分析
- Author:
Shiyan QIU
1
;
Xiaoling LI
;
Ying HUA
;
Shaoxia SUN
Author Information
1. 临沂市人民医院儿内科，临沂 276000
- Keywords:
Baraitser-Winter syndrome;
ACTG1 gene;
Whole exome sequencing
- From:
Chinese Journal of Medical Genetics
2024;41(5):571-576
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical features and genetic etiology of a child with Baraitser-Winter syndrome (BWS).Methods:A BWS child who had sought medical attention at the Linyi People′s Hospital on April 8, 2022 was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples were obtained from the child and his parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 5-year-and-6-month-old male, had typical clinical features of BWS including congenital non-myogenic ptosis, arched eyebrows, wide philtrum, and pointed chin. Neurological symptoms included microcephaly, developmental delay, epilepsy, and deafness. Cranial MRI revealed enlarged frontal lobes, decreased white matter, and hydrocephalus. WES has identified a heterozygous c. 430G>A (p.Asn144Tyr) missense variant in the ACTG1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP3_Moderate+ PP4). Conclusion:The heterozygous c. 430G>A (p.Asn144Tyr) missense variant of the ACTG1 gene probably underlay the pathogenesis of BWS in this child. Above finding has enriched the mutation spectrum of BWS-related genes and provided a basis for clinical diagnosis and genetic counseling.
