A novel frameshift mutation of DVL1‐induced Robinow syndrome: A case report and literature review

Molecular Genetics & Genomic Medicine

Ruolan Hu¹  Yifei Li¹  Yu Qiu¹  Jinrong Li¹ 

[1] Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics West China Second University Hospital, Sichuan University Chengdu China;

关键词: case report;    DVL1;    genomic sequence;    Robinow syndrome;    WNT signaling deficiency;   

DOI  :  10.1002/mgg3.1886

来源: DOAJ

【 摘 要 】

Abstract Background Robinow syndrome is a rare genetic disorder that affects the development of multiple systems. Due to its low prevalence and diversity of phenotypic presentation it has been challenging to definitively characterize features of Robinow syndrome. Methods We performed DNA extraction, whole‐exome sequencing analysis, and mutation analysis of DVL1 to obtain genetic data on the patient. We subsequently analyzed the patient's clinical and genetic data. Results The proband was a 3‐month‐old female infant who suffered from significant global developmental delay and metabolic disorder. The main clinical manifestations included facial dysmorphisms, bilateral dislocation of the hip joint, and hearing impairment. Whole‐exome sequencing of the patient's DNA revealed a heterozygous mutation of c.1620delC in DVL1. Analysis with the MutationTaster application indicated that both were pathogenic (probability = 1), causing frameshift mutations affecting 107 amino acids (p.S542Vfs*107). Significant structural changes were identified in the amino acid sequence after the WNT signaling‐related DEP domain site was predicted using the AlphaFold Protein structure database. The stability of the three main domains was then evaluated using SWISS‐MODEL, and indicated that the mutation did not alter the DIX, PDZ, or DEP domain sequences. Because all reported pathogenic mutations were located near the DEP domain, we speculated that structural changes around the DEP domain may have impaired WNT domain function and WNT signaling, resulting in Robinow syndrome. Conclusion The present case suggests that molecular genetic screening is useful for the diagnosis of developmental disorders, particularly in children with a positive family history. In the current patient all the related pathological variants were located within a narrow locus. This report expands the known manifestations of Robinow syndrome and contributes to refinement of its molecular basis.

【 授权许可】

Unknown