title: Novel COL2A1 variant (c.619G>A, p.Gly207Arg) manifesting as a phenotype similar to progressive pseudorheumatoid dysplasia and spondyloepiphyseal dysplasia, Stanescu type.
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.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205.|Predoctoral Training Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205.
authors.forename: Julie
authors.initials: J
authors.lastname: Jurgens
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205.
authors.forename: Nara
authors.initials: N
authors.lastname: Sobreira
authors.affiliation: Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, 53705.
authors.forename: Peggy
authors.initials: P
authors.lastname: Modaff
authors.affiliation: Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, 53705.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Reiser
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Seo
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea.
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Radiology, Woorisoa Children's Hospital, Seoul, 152-862, Republic of Korea.
authors.forename: Ok Hwa
authors.initials: OH
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, 53705.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Pauli
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D024043:Collagen Type II / Q000235:genetics*; D059472:Exome; D005260:Female; D006801:Humans; D007592:Joint Diseases / Q000151:congenital* / Q000000981:diagnostic imaging / Q000235:genetics; D008297:Male; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II
keywords: PPRD; SED; Stanescu; skeletal dysplasia; spondyloepiphyseal dysplasia tarda with progressive arthropathy; type II collagenopathy