Association of a p.Pro786Leu variant in COL2A1 with mild spondyloepiphyseal dysplasia congenita in a three-generation family

Paul R. Mark, Wilfredo Torres-Martinez, Ralph S. Lachman, David Weaver

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)174-179
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume155
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Lordosis
Coxa Vara
Pubic Bone
Mothers
Uvula
Osteochondrodysplasias
Talus
Calcaneus
Epiphyses
Myopia
Hearing Loss
Proline
Abdomen
Cataract
Genes
Arthritis
Retina
Exons
Spine
Phenotype

Keywords

  • Dwarfism
  • Missense sequence variants
  • Short stature
  • Spondyloepiphyseal dysplasia
  • Type II collagen

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Association of a p.Pro786Leu variant in COL2A1 with mild spondyloepiphyseal dysplasia congenita in a three-generation family. / Mark, Paul R.; Torres-Martinez, Wilfredo; Lachman, Ralph S.; Weaver, David.

In: American Journal of Medical Genetics, Part A, Vol. 155, No. 1, 01.2011, p. 174-179.

Research output: Contribution to journalArticle

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