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RDH12 retinopathy: novel mutations and phenotypic description.
Mol Vis 2011; 17:2706-16MV

Abstract

PURPOSE

To identify patients with autosomal recessive retinal dystrophy caused by mutations in the gene, retinal dehydrogenase 12 (RDH12), and to report the associated phenotype.

METHODS

After giving informed consent, all patients underwent full clinical evaluation. Patients were selected for mutation analysis based upon positive results from the Asper Ophthalmics Leber congenital amaurosis arrayed primer extansion (APEX) microarray screening, linkage analysis, or their clinical phenotype. All coding exons of RDH12 were screened by direct Sanger sequencing. Potential variants were checked for segregation in the respective families and screened in controls, and their pathogenicity analyzed using in silico prediction programs.

RESULTS

Screening of 389 probands by the APEX microarray and/or direct sequencing identified bi-allelic mutations in 29 families. Seventeen novel mutations were identified. The phenotype in these patients presented with a severe early-onset rod-cone dystrophy. Funduscopy showed severe generalized retinal pigment epithelial and retinal atrophy, which progressed to dense, widespread intraretinal pigment migration by adulthood. The macula showed severe atrophy, with pigmentation and yellowing, and corresponding loss of fundus autofluorescence. Optical coherence tomography revealed marked retinal thinning and excavation at the macula.

CONCLUSIONS

RDH12 mutations account for approximately 7% of disease in our cohort of patients diagnosed with Leber congenital amaurosis and early-onset retinal dystrophy. The clinical features of this disorder are highly characteristic and facilitate candidate gene screening. The term RDH12 retinopathy is proposed as a more accurate description.

Authors+Show Affiliations

Department of Genetics, Institute of Ophthalmology, London, UK. d.mackay@ucl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22065924

Citation

Mackay, Donna S., et al. "RDH12 Retinopathy: Novel Mutations and Phenotypic Description." Molecular Vision, vol. 17, 2011, pp. 2706-16.
Mackay DS, Dev Borman A, Moradi P, et al. RDH12 retinopathy: novel mutations and phenotypic description. Mol Vis. 2011;17:2706-16.
Mackay, D. S., Dev Borman, A., Moradi, P., Henderson, R. H., Li, Z., Wright, G. A., ... Moore, A. T. (2011). RDH12 retinopathy: novel mutations and phenotypic description. Molecular Vision, 17, pp. 2706-16.
Mackay DS, et al. RDH12 Retinopathy: Novel Mutations and Phenotypic Description. Mol Vis. 2011;17:2706-16. PubMed PMID: 22065924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RDH12 retinopathy: novel mutations and phenotypic description. AU - Mackay,Donna S, AU - Dev Borman,Arundhati, AU - Moradi,Phillip, AU - Henderson,Robert H, AU - Li,Zheng, AU - Wright,Genevieve A, AU - Waseem,Naushin, AU - Gandra,Mamatha, AU - Thompson,Dorothy A, AU - Bhattacharya,Shomi S, AU - Holder,Graham E, AU - Webster,Andrew R, AU - Moore,Anthony T, Y1 - 2011/10/19/ PY - 2011/06/21/received PY - 2011/10/14/accepted PY - 2011/11/9/entrez PY - 2011/11/9/pubmed PY - 2012/3/1/medline SP - 2706 EP - 16 JF - Molecular vision JO - Mol. Vis. VL - 17 N2 - PURPOSE: To identify patients with autosomal recessive retinal dystrophy caused by mutations in the gene, retinal dehydrogenase 12 (RDH12), and to report the associated phenotype. METHODS: After giving informed consent, all patients underwent full clinical evaluation. Patients were selected for mutation analysis based upon positive results from the Asper Ophthalmics Leber congenital amaurosis arrayed primer extansion (APEX) microarray screening, linkage analysis, or their clinical phenotype. All coding exons of RDH12 were screened by direct Sanger sequencing. Potential variants were checked for segregation in the respective families and screened in controls, and their pathogenicity analyzed using in silico prediction programs. RESULTS: Screening of 389 probands by the APEX microarray and/or direct sequencing identified bi-allelic mutations in 29 families. Seventeen novel mutations were identified. The phenotype in these patients presented with a severe early-onset rod-cone dystrophy. Funduscopy showed severe generalized retinal pigment epithelial and retinal atrophy, which progressed to dense, widespread intraretinal pigment migration by adulthood. The macula showed severe atrophy, with pigmentation and yellowing, and corresponding loss of fundus autofluorescence. Optical coherence tomography revealed marked retinal thinning and excavation at the macula. CONCLUSIONS: RDH12 mutations account for approximately 7% of disease in our cohort of patients diagnosed with Leber congenital amaurosis and early-onset retinal dystrophy. The clinical features of this disorder are highly characteristic and facilitate candidate gene screening. The term RDH12 retinopathy is proposed as a more accurate description. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/22065924/RDH12_retinopathy:_novel_mutations_and_phenotypic_description_ L2 - http://www.molvis.org/molvis/v17/a293/ DB - PRIME DP - Unbound Medicine ER -