Fine mapping of the X-linked recessive congenitalidiopathic nystagmus locus at Xq24-q26.3

[摘要] Purpose: To refine the interval for X-linked congenitalidiopathic nystagmus at Xq24-q26.3 and to evaluate a novel candidategene (Muscleblind-like 3 gene [MBNL3]).Methods: A single pedigree with congenital idiopathicnystagmus (CIN) inherited as an X-linked recessive trait underwentdetailed clinical examination including nystagmology andelectrophysiological investigation in selected subjects. Followingdetailed phenotyping, genotyping was performed using 52 microsatellitemarkers spaced at an average of 5 cM along the X chromosome. Subsequenttwo-point and multipoint linkage analysis were performed and a candidategene was screened for mutations by conventional sequencing.Results: Linkage mapping located the disease gene to a 15.5cMinterval at Xq24-q26.3, between markers DXS1212 and DXS1062 with amaximum two-point LOD score of 4.24 with both markers DXS8044 and DXS994(θ=0). Multipoint analysis indicated a LOD score of 4.54 and acritical gene interval of 8.0 cM. No mutations were found in theMBNL3 gene in this pedigree.Conclusions: We describe a family with an unusual inheritancepattern most consistent with X-linked recessive inheritance with Xinactivation causing manifesting females. We refine the linkage intervalfor X-linked recessive congenital idiopathic nystagmus and excludeMBNL3 as the causative gene in this family.

[学科分类] 生物化学/生物物理