New mutation, P575L, in the GUCY2D gene in a family with autosomal dominant progressive cone degeneration.
ABSTRACT To clinically characterize the retinal abnormalities and identify the mutation causing an autosomal dominant cone degeneration in an African American family.
Clinical characterization of family members using fundus photography, fluorescein angiography, and electrophysiological testing. Standard molecular genetic methods were used, including segregation analysis and DNA sequencing of candidate genes. Genetic mutation screening was performed in 20 individuals: 10 clinically unaffected and 10 affected.
The affected family members had findings consistent with a primary cone degeneration. A novel mutation, P575L, was found in exon 8 of the GUCY2D gene in 12 members of this family.
In addition to finding a previously undescribed mutation in GUCY2D, 2 of the family members who were thought to be unaffected through routine clinical examinations also had this mutation. These findings suggest that autosomal dominant cone degeneration in this family demonstrated age-dependent penetrance, which appears incomplete. This is the first African American family reported with a mutation in GUCY2D. Because the disease in this family and the one we previously described is primarily a cone degeneration, this disease should be more properly classified as cone degeneration and be called cone degeneration 2.
This study helps to expand the phenotype of the disease and help clinicians identify patients with cone degenerations.
Article: A recurrent mutation in GUCY2D associated with autosomal dominant cone dystrophy in a Chinese family.[show abstract] [hide abstract]
ABSTRACT: To identify the genetic locus and mutation responsible for autosomal dominant cone dystrophy (adCOD) in a large Chinese family and to describe the phenotypes of the patients. Genomic DNA and clinical data were collected from the family. Genome-wide linkage analysis was performed to map the disease locus, and Sanger dideoxy sequencing was used to detect the mutation in a candidate gene. Initially, genome-wide linkage analysis mapped the disease to 17p13.1 between D17S831 and D17S799, with a maximum lod score of 2.71 for D17S938 and D17S1852 at theta=0. Sequence analysis of the guanylate cyclase 2D gene (GUCY2D) in the linkage interval detected a recurrent heterozygous mutation, c.2513G>A (p.Arg838His). This mutation was present in all eight patients with adCOD, but neither in any of the six unaffected family members nor in 192 control chromosomes. adCOD in this family is caused by a recurrent mutation in GUCY2D. adCOD can be detected in the first few years after birth in the family by fundus observation and electroretinogram recordings.Molecular vision 01/2011; 17:3271-8. · 2.20 Impact Factor