A Locus For A Chinese Pedigree With Idiopathic Congenital Nystagmus

[ Background and Objective ] Congenital nystagmus is characterized by repetitive,involuntary oscillations of one or double eyes with one or more axes, it can be onset at birth or in the first few months. It may be divided into congenital motor nystagmus (without detectable underlying pathology) and congenital sensory nystagmus (onset at birth associated with ocular disease). Various patterns of inheritance for CN have been described, including X-linked dominant and X-linked recessive (MIM 310700), autosomal dominant (MIM 164100) and autosomal recessive (MIM 257400). X linked inheritance is the most common. And the associated genes for CN have been at least mapped on three loci: Xq26-27, Xp 11.3-11.4, 6p 12. The additional locus remains to be identificated. But no pathogenetic gene has been cloned. To refine the location of CMN, we had research on a Chinese pedigree of CMN through genescan and linkage analysis.[Method] We have identified an independent five generations pedigree with CMN came from province Zhejiang. DNA was prepared by the standard procedure.20 microsatellite markers containing short tracts of (CA) ?repeats were chosen from the UCSC linkage map, which were previously used for fine mapping of the locus for CMN on X chromosome. Two-point LOD scores between the disease locus and markers were calculated by the MLINK program of LINKAGE package (version 5.1). Multi-point linkage analysiswere used to estimate the optimal position with GENEHUNTER. The X-inactivation status of women were investigated by PCR amplification of apolymorphic site at the human androgen receptor (AR) locus. SLC9A6 and FGF13, as candidate genes, were sequenced.[Results] Typical features of X linked dominant inheritance were presented in this pedigree. The results of linkage analysis for chromosome Xp didn't support linkage; The maximum LOD score was 2 on DXS1192 and large for 1 near DXS1192. The maximum multipoint LOD score in multipoint linkage analysis was obtained around DXS8033 and DXS8043. No correlation was observed between the X-inactivation pattern and phenotye. No mutation of SLC9A6 and FGF13 was found in two patients from this pedigree.[Conclusions] we have definedX-linked dominant congenital idiopathic nystagmus, an X-linked, truly dominant condition that has not previously been reported. This study raise the possibility that the region Xq26-27 is a common locus for CMN and bring us closer to the identification of a gene responsible for X-linked CMN. We also confirmed the genetic heterogeneity in X-linked CMN.