| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12q13.11 | ?Vitreoretinopathy with phalangeal epiphyseal dysplasia | 619248 | Autosomal dominant | 3 | COL2A1 | 120140 |
A number sign (#) is used with this entry because of evidence that vitreoretinopathy with phalangeal epiphyseal dysplasia (VPED) is caused by heterozygous mutation in the COL2A1 (120140) on chromosome 12q13. One such family has been reported.
Vitreoretinopathy with phalangeal epiphyseal dysplasia (VPED) is an autosomal dominant disorder characterized by rhegmatogenous retinal detachment, premature arthropathy, and development of phalangeal epiphyseal dysplasia, resulting in brachydactyly. Stature is normal, and high myopia, cleft palate, and midfacial hypoplasia are absent (Richards et al., 2002).
Richards et al. (2002) described a white British family with dominantly inherited rhegmatogenous retinal detachment, premature hand arthropathy, and development of phalangeal epiphyseal dysplasia resulting in brachydactyly. The patients had normal stature and normal facies without the midface hypoplasia usually associated with Stickler syndrome (see 108300). None of the affected subjects had cleft palate. The vitreoretinal changes were characteristic, with extensive lattice retinopathy and disorganized vitreous lamellae. There was no evidence of high myopia as seen in Stickler syndrome. One family member (III.8) had bilateral retinal detachment at age 13 years, resulting in blindness. Patients reported pain and swelling of the joints in their hands beginning at puberty. In the most severely affected individuals, fingers were recalled as being short since early childhood. Feet were normal in all patients. The majority of affected family members had shortening of all phalanges, whereas in severe cases, there was additional involvement of metacarpal and carpal bones as well as the distal epiphyses of the radius and ulna. Epiphyseal changes in the hips were variable, with hip replacement surgery required for those with severe, premature osteoarthropathy.
In a British family segregating VPED, Richards et al. (2002) found linkage of the disorder to the COL2A1 gene on chromosome 12q13 (maximum lod of 5.4 at 0 recombination with D12S361).
The transmission pattern of VPED in the family reported by Richards et al. (2002) was consistent with autosomal dominant inheritance.
By molecular analysis of the COL2A1 gene in a British family segregating VPED, Richards et al. (2002) identified a heterozygous single base change (G-A) in exon 52, which resulted in a gly1105-to-asp (G1105D; 120140.0037) substitution in the C-propeptide region. The mutation segregated with the disorder in the family. The mutation occurred in a region that is highly conserved in all fibrillar collagen molecules.
Richards, A. J., Morgan, J., Bearcroft, P. W. P., Pickering, E., Owen, M. J., Holmans, P., Williams, N., Tysoe, C., Pope, F. M., Snead, M. P., Hughes, H. Vitreoretinopathy with phalangeal epiphyseal dysplasia, a type II collagenopathy resulting from a novel mutation in the C-propeptide region of the molecule. J. Med. Genet. 39: 661-665, 2002. [PubMed: 12205109] [Full Text: https://doi.org/10.1136/jmg.39.9.661]