Analysis of OFD1 gene variation in a child with Oral-facial-digital syndrome
10.3760/cma.j.cn511374-20250108-00016
- VernacularTitle:OFD1基因变异所致口-面-指(趾)综合征1例患儿的临床及遗传学分析
- Author:
Liya ZHANG
1
;
Yu LIU
;
Lulu YAN
;
Jin Xia MIN
;
Lijiao ZHU
;
Ting YANG
;
Lili CHEN
;
Yingbo CUI
Author Information
1. 宁波大学附属妇女儿童医院新生儿中心，宁波 315012
- Publication Type:Journal Article
- Keywords:
Orofaciodigital Syndromes;
Mutation, gene;
Multilocus sequence typing;
Genetic variation;
OFD1 gene;
Genetic variation;
Next-generation sequencing
- From:
Chinese Journal of Medical Genetics
2025;42(6):707-712
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ).Method:A child with OFDSⅠ who received treatment at the Women and Children′s Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children′s Hospital (Ethic No.: EC 2024-063).Results:The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c. 710dup(p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child′s parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+ PS4_Moderate+ PM2-Supporting+ PM6_Supporting+ PP4). Conclusion:Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c. 710dup(p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.
