| First Author | Faden M | Year | 2015 |
| Journal | Am J Hum Genet | Volume | 97 |
| Issue | 4 | Pages | 608-15 |
| PubMed ID | 26365341 | Mgi Jnum | J:230757 |
| Mgi Id | MGI:5763714 | Doi | 10.1016/j.ajhg.2015.08.007 |
| Citation | Faden M, et al. (2015) Identification of a Recognizable Progressive Skeletal Dysplasia Caused by RSPRY1 Mutations. Am J Hum Genet 97(4):608-15 |
| abstractText | Skeletal dysplasias are highly variable Mendelian phenotypes. Molecular diagnosis of skeletal dysplasias is complicated by their extreme clinical and genetic heterogeneity. We describe a clinically recognizable autosomal-recessive disorder in four affected siblings from a consanguineous Saudi family, comprising progressive spondyloepimetaphyseal dysplasia, short stature, facial dysmorphism, short fourth metatarsals, and intellectual disability. Combined autozygome/exome analysis identified a homozygous frameshift mutation in RSPRY1 with resulting nonsense-mediated decay. Using a gene-centric "matchmaking" system, we were able to identify a Peruvian simplex case subject whose phenotype is strikingly similar to the original Saudi family and whose exome sequencing had revealed a likely pathogenic homozygous missense variant in the same gene. RSPRY1 encodes a hypothetical RING and SPRY domain-containing protein of unknown physiological function. However, we detect strong RSPRY1 protein localization in murine embryonic osteoblasts and periosteal cells during primary endochondral ossification, consistent with a role in bone development. This study highlights the role of gene-centric matchmaking tools to establish causal links to genes, especially for rare or previously undescribed clinical entities. |
