Alternative titles; symbols
ORPHA: 99001; DO: 0060864;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q31.2 | Macular dystrophy, patterned, 2 | 608970 | Autosomal dominant | 3 | CTNNA1 | 116805 |
A number sign (#) is used with this entry because of evidence that patterned macular dystrophy-2 (MDPT2) is caused by heterozygous mutation in the CTNNA1 gene (116805) on chromosome 5q31.
Butterfly-shaped pigmentary macular dystrophy is an autosomal dominant eye disease characterized by bilateral accumulation of pigment in the macular area that resembles the wings of a butterfly (summary by van Lith-Verhoeven et al., 2003).
For a general phenotypic description and a discussion of genetic heterogeneity of patterned macular dystrophy, see 169150.
Deutman et al. (1970) described 4 of 5 brothers and the son of 1 of them with a peculiar, bilateral, butterfly-shaped pigment dystrophy of the fovea. Although electrooculogram indicated a diffuse abnormality of the retina, there was little or no impairment of vision. The disorder was characterized by abnormal pigment at the level of the retinal pigment epithelium (RPE). This material is yellow, white, or black, and often accumulates in an unusual configuration consisting of 3 to 5 'arms' or 'wings' that resemble the wings of a butterfly. The material can be detected in some patients in the second decade of life, but affected individuals most commonly become symptomatic in their late twenties or early thirties.
Van Lith-Verhoeven et al. (2003) performed linkage studies in the Dutch family in which butterfly-shaped pigmentary macular dystrophy was first described (Deutman et al., 1970) and excluded involvement of 44 loci known to be involved in retinal dystrophies, the ROM1 gene (180721), and the RDS gene (PRPH2; 179605). Den Hollander et al. (2004) performed a genomewide linkage scan in this family and identified a novel locus for butterfly-shaped macular dystrophy on chromosome 5q21.2-q33.2 (maximum multipoint lod score of 4.05 between markers D5S433 and D5S410). The critical interval spans 46 cM (52 Mb) and contains the PDE6A gene (180071). Sequence analysis of PDE6A showed no pathologic mutation.
In the large Dutch family with patterned macular dystrophy mapping to chromosome 5q21-q33, originally described by Deutman et al. (1970), Saksens et al. (2016) performed whole-exome sequencing and identified a heterozygous missense mutation in the CTNNA1 gene (L318S; 116805.0001). The mutation segregated fully with disease in the family and was not found in 162 ancestry-matched controls or in the Exome Variant Server database. Sequencing CTNNA1 in 93 unrelated individuals with butterfly-shaped pigment dystrophy and other pattern dystrophies identified 2 more missense mutations that segregated with disease: I431M (116805.0002) in a Dutch mother and son, and E307K (116805.0003) in a Belgian mother and daughter.
den Hollander, A. I., van Lith-Verhoeven, J. J. C., Kersten, F. F. J., Heister, J. G. A. M., de Kovel, C. G. F., Deutman, A. F., Hoyng, C. B., Cremers, F. P. M. Identification of novel locus for autosomal dominant butterfly shaped macular dystrophy on 5q21.2-q33.2. J. Med. Genet. 41: 699-702, 2004. [PubMed: 15342701] [Full Text: https://doi.org/10.1136/jmg.2004.019562]
Deutman, A. F., van Blommestein, J. D. A., Henkes, H. E., Waardenburg, P. J., Solleveld-van Driest, E. Butterfly-shaped pigment dystrophy of the fovea. Arch. Ophthal. 83: 558-569, 1970. [PubMed: 5442145] [Full Text: https://doi.org/10.1001/archopht.1970.00990030558006]
Saksens, N. T. M., Krebs, M. P., Schoenmaker-Koller, F. E., Hicks, W., Yu, M., Shi, L., Rowe, L., Collin, G. B., Charette, J. R., Letteboer, S. J., Neveling, K., van Moorsel, T. W., and 13 others. Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed retinal pigment epithelium integrity. Nature Genet. 48: 144-151, 2016. [PubMed: 26691986] [Full Text: https://doi.org/10.1038/ng.3474]
van Lith-Verhoeven, J. J. C., Cremers, F. P. M., van den Helm, B., Hoyng, C. B., Deutman, A. F. Genetic heterogeneity of butterfly-shaped pigment dystrophy of the fovea. Molec. Vis. 9: 138-143, 2003. [PubMed: 12724643]