Evidence for a Novel Autosomal Dominant Retinitis Pigmentosa Linked to Chromosome 1p22.1-q12 in a Chinese Family

Abstract

Purpose: To identify the causative genetic locus in a Chinese autosomal dominant retinitis pigmentosa (adRP) family that contained seven affected members in three generations.

Methods: After clinical diagnosis and exclusion of all mapped genes and loci, the SLINK program was used to simulate the maximum logarithm of the likelihood ratio (LOD) score for a linkage study in this small family. A genome-wide scan was performed using microsatellite markers at 10 cM intervals. Two-point and multipoint LOD scores were calculated, and haplotypes were constructed.

Results: The H11 family clinical presentation included an early onset of night blindness, a progressive loss of the peripheral visual field, typical retinitis pigmentosa (RP) fundus changes, and a cataract complication. A maximum two-point LOD score of 2.54 (θ = 0) was found at markers D1S2739, D1S457, D1S187, D1S189, and D1S305, and multipoint linkage analysis yielded a maximum LOD score of 2.54 for marker D1S187. These LOD scores were the closest to the maximum simulated LOD score. Haplotype analysis revealed that this form of adRP segregates with a 38.25 cM region that spanned 50 Mb on chromosome 1p22.1-q12.

Conclusions: Although this locus overlaps the RP19 locus caused by mutations in ABCA4 and the RP32 locus, both are inherited in an autosomal recessive mode rather than the autosomal dominant mode of inheritance found in the H11 family. The identification of this potential new locus for adRP further confirms the high level of heterogeneity for RP.

KEYWORDS::

• Autosomal dominant retinitis pigmentosa
• Candidate genes
• Haplotype
• Linkage analysis
• LOD score

ACKNOWLEDGMENTS

The authors are grateful to the participating members in family H11 and are sincerely thankful to Dr. Lisong Shi, who is at the Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China, for his professional guidance in software. The authors also wish to thank Dr. Guibo Song, who is a colleague, for his kind suggestions. This work was supported by the National Natural Science Foundation of China (3067201 and 30770658).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.