Title | Novel COL2A1 variant (c.619G>A, p.Gly207Arg) manifesting as a phenotype similar to progressive pseudorheumatoid dysplasia and spondyloepiphyseal dysplasia, Stanescu type. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Jurgens, J, Sobreira, N, Modaff, P, Reiser, CA, Seo, SHyun, Seong, M-W, Park, SSup, Kim, OHwa, Cho, T-J, Pauli, RM |
Journal | Hum Mutat |
Volume | 36 |
Issue | 10 |
Pagination | 1004-8 |
Date Published | 2015 Oct |
ISSN | 1098-1004 |
Keywords | Adolescent, Adult, Child, Collagen Type II, Exome, Female, Humans, Joint Diseases, Male, Osteochondrodysplasias, Pedigree, Polymorphism, Single Nucleotide, Radiography, Sequence Analysis, DNA |
Abstract | Progressive pseudorheumatoid dysplasia (PPRD) is a rare, autosomal-recessive condition characterized by mild spondyloepiphyseal dysplasia (SED) and severe, progressive, early-onset arthritis due to WISP3 mutations. SED, Stanescu type, is a vaguely delineated autosomal-dominant dysplasia of unknown genetic etiology. Here, we report three individuals from two unrelated families with radiological features similar to PPRD and SED, Stanescu type who share the same novel COL2A1 variant and were matched following discussion at an academic conference. In the first family, we performed whole-exome sequencing on three family members, two of whom have a PPRD-like phenotype, and identified a heterozygous variant (c.619G>A, p.Gly207Arg) in both affected individuals. Independently, targeted sequencing of the COL2A1 gene in an unrelated proband with a similar phenotype identified the same heterozygous variant. We suggest that the p.Gly207Arg variant causes a distinct type II collagenopathy with features of PPRD and SED, Stanescu type. |
DOI | 10.1002/humu.22839 |
Alternate Journal | Hum. Mutat. |
PubMed ID | 26183434 |
PubMed Central ID | PMC4575260 |
Grant List | T32 GM007814 / GM / NIGMS NIH HHS / United States U54 HG006542 / HG / NHGRI NIH HHS / United States 1U54HG006542 / HG / NHGRI NIH HHS / United States T32GM07814 / GM / NIGMS NIH HHS / United States |