Identification of a novel pathogenic variant in the MYH3 gene in a five‐generation family with CPSFS1A (Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A)
| Autor: | Si‐Wen Wang, Wen-Qi Chen, Shao‐Xiong Wang, Ya‐Dong Yu, Qing Guo, Mei Yu, Jing Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Proband Contracture lcsh:QH426-470 Genetic counseling Prenatal diagnosis 030105 genetics & heredity Biology Pterygium Thoracic Vertebrae 03 medical and health sciences symbols.namesake INDEL Mutation CPSFS1A MYH3 Genetics medicine Humans Abnormalities Multiple distal arthrogryposis Musculoskeletal Diseases Molecular Biology Gene Genetics (clinical) Exome sequencing Aged Arthrogryposis Sanger sequencing Fetus Lumbar Vertebrae Myosin Heavy Chains Syndrome Original Articles Middle Aged Pedigree lcsh:Genetics 030104 developmental biology Scoliosis Synostosis symbols Female Original Article whole‐exome sequencing medicine.symptom |
| Zdroj: | Molecular Genetics & Genomic Medicine, Vol 8, Iss 10, Pp n/a-n/a (2020) Molecular Genetics & Genomic Medicine |
| ISSN: | 2324-9269 |
| DOI: | 10.1002/mgg3.1440 |
| Popis: | Background Distal arthrogryposis (DA) is a group of rare Mendelian conditions that demonstrate heterogeneity with respect to genetics and phenotypes. Ten types of DAs, which collectively involve six genes, have been reported. Among them, the MYH3 gene causes several types of arthrogryposis conditions and therefore has a pivotal role in the skeletal and muscle development of the fetus. For this study, we recruited a five‐generation Chinese family with members presenting DA features and phenotypic variability. Further clinical study characterized it as CPSFS1A (Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A). Methods Genomic DNA was extracted from eight family members, including one fetus. Whole‐exome sequencing (WES) was then conducted on the proband's sample, followed by Sanger sequencing as validation for each of the participants. In silico analysis was performed. Western blotting (WB) detection and pathological staining were conducted on skeletal muscle tissue of the induced fetus after prenatal diagnosis. Results A novel heterozygous pathogenic variant, namely NM_002470.3: c.3044_3047delinsTCAATTTGTT: p.E1015_D1016delinsVNLF in the MYH3 gene, was identified and shown to be cosegregated with the condition in the subject family. This variant resulted in the replacement of amino‐acid residues E1015 and D1016 by a string of VNLFs. The pregnancy was selectively terminated because the fetus was genetically affected. However, the WB and pathological results did not indicate a significant change in the norm. Conclusions Our study expanded the variant spectrum of CPSFS1A, in addition to which it provided solid evidence for the appropriateness of genetic counseling and pregnancy management for the family. The results may also provide further insight into the molecular mechanism of MYH3. We have reported for the first time in a Chinese five‐generation family, a novel pathogenic variant c.3044_3047delinsTCAATTTGTT in the MYH3 gene causing CPSFS1A. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|