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Association of a p.Pro786Leu variant in COL2A1 with mild spondyloepiphyseal dysplasia congenita in a three‐generation family
Author(s) -
Mark Paul R.,
TorresMartinez Wilfredo,
Lachman Ralph S.,
Weaver David D.
Publication year - 2011
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33762
Subject(s) - proband , short stature , osteochondrodysplasia , biology , genetics , exon , coxa vara , anatomy , medicine , gene , mutation , endocrinology , femur , paleontology
Heterozygous sequence variants of the COL2A1 gene cause a phenotypic spectrum collectively called type II collagenopathies. Here, we describe a COL2A1 sequence variant, c.2957C>T, p.Pro986Leu in the triple helical domain, which is a Y‐position substitution in exon 41 of the repeating triplet sequence Gly‐X‐Y of the proα1(II) chain. This sequence variant was associated with a mild spondyloepiphyseal dysplasia phenotype in three individuals in a three‐generation family. On clinical examination at the age of 19 months, the proband had a flat face, bifid uvula, and a protruding abdomen. Radiographically, he had rhizomelia, mesomelia, and ovoid‐shaped vertebrae. He also had absent mineralization of the epiphyses, the os pubis, tali, and calcanei. His mother had myopia, mild lumbar lordosis, and mild coxa vara. She had a detached retina repaired at age 24 years. The maternal grandmother had cataracts but has had no kyphoscoliosis or lordosis. All three had disproportionate short stature. None had arthritis or hearing loss. The sequence variant in this family is the only reported Y‐position proline substitution in the triple helical domain (Gly‐X‐Y) of the proα1(II) coded by the COL2A1 gene. © 2010 Wiley‐Liss, Inc.