Abstract | BACKGROUND: METHODS: Patients referred to the national Stickler syndrome diagnostic service for England, UK were assessed clinically and subsequently sequenced for mutations in COL11A1. Additional in silico and functional studies to assess the effect of sequence variants on pre-mRNA processing and collagen structure were performed. RESULTS: In three different families, heterozygous COL11A1 biallelic null, null/missense or silent/missense mutations, were found. They resulted in a recessive form of type 2 Stickler syndrome characterised by particularly profound hearing loss and are clinically distinct from the recessive types 4 and 5 variants of Stickler syndrome. One mutant allele in each family is capable of synthesising a normal α1(XI) procollagen molecule, via variable pre-mRNA processing. CONCLUSION: This new variant has important implications for molecular diagnosis and counselling families with type 2 Stickler syndrome.
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Authors | Allan J Richards, Gregory S Fincham, Annie McNinch, David Hill, Arabella V Poulson, Bruce Castle, Melissa M Lees, Anthony T Moore, John D Scott, Martin P Snead |
Journal | Journal of medical genetics
(J Med Genet)
Vol. 50
Issue 11
Pg. 765-71
(Nov 2013)
ISSN: 1468-6244 [Electronic] England |
PMID | 23922384
(Publication Type: Journal Article)
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Chemical References |
- COL11A1 protein, human
- Collagen Type XI
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Topics |
- Adult
- Alternative Splicing
- Amino Acid Sequence
- Child, Preschool
- Collagen Type XI
(deficiency, genetics)
- Connective Tissue Diseases
(genetics)
- Female
- Hearing Loss
(genetics)
- Humans
- Infant
- Male
- Molecular Sequence Data
- Mutation
- Pedigree
- Vitreous Detachment
(genetics)
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