Affiliation:
1. State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock (RRBGL) Inner Mongolia University Hohhot 010070 China
2. Department of Genetics Inner Mongolia Maternity and Child Health Care Hospital Hohhot 010010 China
3. Department of Ultrasonic Medicine Inner Mongolia Maternity and Child Health Care Hospital Hohhot 010010 China
Abstract
AbstractBackgroundEllis–van Creveld (EvC) syndrome, caused by variants in EVC, is a rare genetic skeletal dysplasia. Its clinical phenotype is highly diverse. EvC syndrome is rarely reported in prenatal stages because its presentation overlaps with other diseases.MethodsA Chinese pedigree diagnosed with EvC syndrome was enrolled in this study. Whole‐exome sequencing (WES) was applied in the proband to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in family members. Minigene experiments were applied.ResultsWES identified a homozygous variant (NM_153717.3:c.153_174 + 42del) in EVC which was inherited from the heterozygous parents and confirmed by Sanger sequencing. Further experiments demonstrated that this variant disrupts the canonical splicing site and produces a new splicing site at NM_153717.3: c.‐164_174del, which ultimately leads to a 337 bp deletion at the 3′ end of exon 1 and loss of the start codon.ConclusionThis is the first reported case of EvC syndrome based on a splicing variant and detailed delineation of the aberrant splicing effect in the fetus. Our study demonstrates the pathogenesis of this new variant, expands the spectrum of EVC mutations, and demonstrates that WES is a powerful tool in the clinical diagnosis of diseases with genetic heterogeneity.
Subject
Genetics (clinical),Genetics,Molecular Biology
Cited by
1 articles.
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