Phenotype and genotype analysis of a pedigree affected with Joubert syndrome due to variant of TMEM237 gene.
10.3760/cma.j.cn511374-20201015-00722
- Author:
Shandan CUI
1
;
Haijuan LOU
;
Haijun YIN
;
Fangfang GENG
;
Ning LI
;
Lirong MA
Author Information
1. Prenatal Diagnosis Center, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010010, China. 1024475770@qq.com.
- Publication Type:Journal Article
- MeSH:
Abnormalities, Multiple/genetics*;
Cerebellum/abnormalities*;
Eye Abnormalities;
Female;
Genotype;
Humans;
Kidney Diseases, Cystic;
Mutation;
Pedigree;
Phenotype;
Pregnancy;
Retina/abnormalities*
- From:
Chinese Journal of Medical Genetics
2021;38(12):1211-1215
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the pathogenesis of two siblings (including a fetus) from a pedigree affected with Joubert syndrome.
METHODS:Peripheral blood samples of the proband and his parents as well as amniotic fluid and abortion tissues of the fetus were collected. Part of the samples were used for the extraction of DNA, and whole exome sequencing (WES) was carried out to screen potential variants in the proband and his parents. Suspected variants were subjected to bioinformatics analysis with consideration of the clinical phenotype, and were verified by Sanger sequencing of the proband, fetus and their parents.The remainders were used for the extraction of RNA, and the mechanism of splicing variant was validated by reverse transcription-PCR (RT-PCR).
RESULTS:WES showed that both patients have carried c.175C>T (p.R59X) and c.553+1G>A compound heterozygous variants of the TMEM237 gene. Among these, c.175C>T was a nonsense mutation inherited from the asymptomatic mother, while c.553+1G>A was an alternative splicing mutation inherited from the asymptomatic father. RT-PCR showed that this variant has resulted in aberrant splicing by exon skipping.
CONCLUSION:The compound heterozygous variants of the TMEM237 gene probably underlay the etiology of Joubert syndrome in this pedigree. Above finding has enriched the phenotype and variant spectrum of the TMEM237 gene, and facilitated genetic counseling and prenatal diagnosis for the family.
