Genetic analysis of a child with DIGFAN syndrome due to variant of MORC2 gene
10.3760/cma.j.cn511374-20221205-00841
- VernacularTitle:MORC2基因新发变异导致DIGFAN综合征1例的遗传学分析
- Author:
Bobo XIE
1
;
Xin FAN
;
Xianda WEI
;
Baoheng GUI
;
Xiaojiao WEI
;
Yunting MA
;
Shihan FENG
;
Yujun CHEN
Author Information
1. 广西医科大学第二附属医院遗传与基因组医学中心，南宁 530007
- Keywords:
Narvous system diseases;
Developmental delay;
Impaired growth;
Dysmorphic facies;
Axonal neuropathy;
MORC2 gene;
De novo variant;
Child
- From:
Chinese Journal of Medical Genetics
2024;41(2):234-238
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN).Methods:A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c. 800T>C (p.Leu267Pro) variant of the MORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 800T>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). Conclusion:The MORC2: c. 800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.
