Case report: Analysis of a gene variant and prenatal diagnosis in a family with megalencephalic leukoencephalopathy with subcortical cysts

Frontiers in Neurology

Neurology

Tiantian He¹  Xi Chen¹  Xuemei Zhang¹  Qiang Yao²  Haibo Qu³  Xiaotang Cai⁴ 

[1] Department of Medical Genetics and Prenatal Diagnosis Center, West China Second University Hospital, Sichuan University, Chengdu, China;Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China;Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China;Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China;Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China;Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China;Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China;Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China;Department of Rehabilitation, West China Second University Hospital, Sichuan University, Chengdu, China;

关键词: MLC;    MLC1;    leukodystrophy;    splice mutation;    clinical phenotype;    prenatal diagnosis;    genetic counseling;   

DOI  :  10.3389/fneur.2023.1253398

 received in 2023-07-05, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare inherited cerebral white matter disorder in children. Pathogenic variations in the causative gene MLC1 are found in approximately 76% of patients and are inherited in an autosomal recessive manner. In this study, we identified an IVS2 + 1delG variant in MLC1 in the firstborn girl of a pregnant woman who has the clinical features of MLC, including macrocephaly, motor development delay, progressive functional deterioration, and myelinopathy, whereas no obvious subcortical cysts were observed by magnetic resonance imaging of the brain. The proband is homozygous for the IVS2 + 1delG mutation, which was inherited from the parents. This variant disrupts the donor splice site, causing an abnormal transcript that results in a premature termination codon and produces a truncated protein, which was confirmed to affect splicing by MLC1 cDNA analysis. This variant was also detected in family members, and a prenatal diagnosis for the fetus was undertaken. Eventually, the couple gave birth to an unaffected baby. Furthermore, we conducted a long-term follow-up of the proband’s clinical course. This report improves our understanding of the genetic and phenotypic characteristics of MLC and provides a new genetic basis for prenatal diagnosis and genetic counseling.

【 授权许可】

Unknown   
Copyright © 2023 Chen, Qu, Yao, Cai, He and Zhang.