A novel dominant COL11A1 mutation resulting in a severe skeletal dysplasia. Issue 10 (4th August 2014)

• Record Type: Journal Article
• Authors: Hufnagel, Sophia B.; Weaver, K Nicole; Hufnagel, Robert B.; Bader, Patricia I.; Schorry, Elizabeth K.; Hopkin, Robert J.
• Is Part Of: American journal of medical genetics. Volume 164:Issue 10(2014.)
• Page Start: 2607
• Page End: 2612
• Publication Date: 2014-08-04
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36688
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36688-sec-0001" sec-type="section"> <p>Mutations in the type XI collagen alpha‐1 chain gene (<italic>COL11A1</italic>) cause a change in protein structure that alters its interactions with collagens II and V, resulting in abnormalities in cartilage and ocular vitreous. The most common type XI collagenopathies are dominantly inherited Stickler or Marshall syndromes, while severe recessive skeletal dysplasias, such as fibrochondrogenesis, occur less frequently. We describe a family with a severe skeletal dysplasia caused by a novel dominantly inherited <italic>COL11A1</italic> mutation. The siblings each presented with severe myopia, hearing loss, micromelia, metaphyseal widening of the long bones, micrognathia, and airway compromise requiring tracheostomy. The first child lived for over 2 years, while the second succumbed at 5 months of age. Their mother has mild rhizomelic shortening of the limbs, brachydactyly, and severe myopia. Sequencing of <italic>COL11A1</italic> revealed a novel deleterious heterozygous mutation in <italic>COL11A1</italic> involving the triple helical domain in both siblings, and a mosaic mutation in their mother, indicating germline mosaicism with subsequent dominant inheritance. These are the first reported individuals with a dominantly inherited mutation in <italic>COL11A1</italic> associated with a severe skeletal dysplasia. The skeletal involvement is similar to, yet milder than fibrochondrogenesis and allowed for survival beyond the perinatal period. These cases highlight both a novel dominant <italic>COL11A1</italic> mutation causing a significant skeletal dysplasia and the phenotypic heterogeneity of collagenopathies. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>