A novel locus for autosomal dominant congenital motor nystagmus mapped to 1q31-q32.2 between D1S2816 and D1S2692

Abstract

Congenital motor nystagmus (CMN) is characterized by bilateral involuntary ocular oscillation without any other underlying ocular or systemic diseases. An autosomal dominant CMN was identified in a large Chinese family where all patients had nystagmus since infancy. The nystagmus in the family is independent of any known ocular or systemic diseases. After exclusion of known CMN loci, a genome-wide scan was performed by genotyping microsatellite markers at about 10 cM intervals, together with two-point linkage analysis. Exome sequencing was used to screen coding exons of well-annotated genes. Sanger-dideoxy sequencing was used to verify candidate variations inside the linkage interval. Congenital motor nystagmus in this family shows linkage to markers in a 11.39 Mb (12.1 cM) region on chromosome 1q31-q32.2 between D1S2816 and D1S2692. All nine markers in the linkage interval gave positive lod scores, with D1S2655 and D1S2636 yielding lod scores of 5.16 and 5.18, respectively, at θ = 0. No causative mutation in the linkage interval was identified by exome sequencing of gDNA from four patients. A linkage study of additional families and further analysis of candidate genes may ultimately lead to identification of the gene responsible for dominantly inherited CMN.