A Genomic Approach to Delineating the Occurrence of Scoliosis in Arthrogryposis Multiplex Congenita

• Published in: Genes 2021-07, Vol.12 (7), p.1052
• Main Authors: Latypova, Xenia, Creadore, Stefan Giovanni, Dahan-Oliel, Noémi, Gustafson, Anxhela Gjyshi, Wei-Hung Hwang, Steven, Bedard, Tanya, Shazand, Kamran, van Bosse, Harold J P, Giampietro, Philip F, Dieterich, Klaus
• Format: Article
• Language: English
• Subjects: Akinesia; Animal models; Arthrogryposis; Arthrogryposis - complications; Copy number; DNA Copy Number Variations; Foot diseases; Gene Expression Profiling; Gene Expression Regulation; Gene regulation; Genes; Genetic Markers; Genomics; Genomics - methods; Genotype & phenotype; Humans; Ion channels; Ontogeny; Ontology; Patients; Phenotype; Phenotypes; Scoliosis; Scoliosis - diagnosis; Scoliosis - etiology; Scoliosis - genetics; Software; Therapeutic targets; Transcription
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12071052

Arthrogryposis multiplex congenita (AMC) describes a group of conditions characterized by the presence of non-progressive congenital contractures in multiple body areas. Scoliosis, defined as a coronal plane spine curvature of ≥10 degrees as measured radiographically, has been reported to occur in approximately 20% of children with AMC. To identify genes that are associated with both scoliosis as a clinical outcome and AMC, we first queried the DECIPHER database for copy number variations (CNVs). Upon query, we identified only two patients with both AMC and scoliosis (AMC-SC). The first patient contained CNVs in three genes ( , , and , while the second case had a CNV in . Looking into small variants, using a combination of Human Phenotype Ontogeny and literature searching, 908 genes linked with scoliosis and 444 genes linked with AMC were identified. From these lists, 227 genes were associated with AMC-SC. Ingenuity Pathway Analysis (IPA) was performed on the final gene list to gain insight into the functional interactions of genes and various categories. To summarize, this group of genes encompasses a diverse group of cellular functions including transcription regulation, transmembrane receptor, growth factor, and ion channels. These results provide a focal point for further research using genomics and animal models to facilitate the identification of prognostic factors and therapeutic targets for AMC.