Vanita Vanita, Singh Jai Rup, Hejtmancik James Fielding, Nuernberg Peter, Hennies Hans Christian, Singh Daljit, Sperling Karl
Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, Punjab, India.
Mol Vis. 2006 May 22;12:518-22.
The molecular characterization of an Indian family having 10 members in four generations affected with a unique fan-shaped cataract-microcornea syndrome.
Detailed family history and clinical data were recorded. A genome-wide screening by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was carried out. Mutation screening was performed in the candidate gene by bi-directional sequencing of amplified products.
The cataract-microcornea locus in this family was mapped to a 23.5 cM region on chromosome 21q22.3. Direct sequencing of the candidate gene CRYAA revealed a heterozygous C>T transition resulting in the substitution of the highly conserved arginine at position 116 by cysteine (R116C).
This study provides the report of mapping a locus for syndromal cataract (cataract-microcornea syndrome) on 21q22.3. The mutation observed in CRYAA in the present family highlights the phenotypic heterogeneity of the disorder in relation to the genotype, as an identical mutation has previously been reported in an American family with a different type of cataract. The "fan-shaped cataract" observed in the present family has not been reported before.
对一个四代共10名成员患有一种独特的扇形白内障-小角膜综合征的印度家族进行分子特征分析。
记录详细的家族史和临床数据。采用400多个微卫星标记，结合多点对数优势计分法和单倍型分析，通过两点连锁分析进行全基因组筛查。对候选基因的扩增产物进行双向测序，以进行突变筛查。
该家族的白内障-小角膜基因座定位于21号染色体q22.3上一个23.5厘摩的区域。对候选基因CRYAA进行直接测序发现了一个杂合的C>T转换，导致第116位高度保守的精氨酸被半胱氨酸取代（R116C）。
本研究报告了在21q22.3上定位一个综合征性白内障（白内障-小角膜综合征）基因座。本家族中在CRYAA基因中观察到的突变突出了该疾病在基因型方面的表型异质性，因为之前在一个患有不同类型白内障的美国家族中也报道了相同的突变。本家族中观察到的“扇形白内障”此前未见报道。
