Search for a gene for cataract and craniofacial anomalie

在一个近亲交配的沙特阿拉伯家庭中发现了一种新的畸形综合征，伴有迟闭合的颧骨和缝合性白内障(颅晶状体缝合不良)。最突出的特征是穹窿和缝线关闭失败；出生时，由于开放的矢状缝和中缝，前穹窿较大。第二个主要特征是后部Y形缝线的白内障，它是先天性的或随时间发展的。 遗传病研究中心(CIDR)使用387个标记对21个DNA样本进行了全基因组筛查，并确定了几个候选区域。缩小这些候选区域的侧翼标记的基因分型也已经完成。 假设常染色体隐性遗传的两点LOD得分分析表明与染色体14q13-q21上的标记连锁。使用SIBPAL进行的独立于模型的分析证实了与同一区域的联系。单倍型分析表明，在标记D14S306-ATA38D06之间，所有受累个体均为纯合子，其中两个重组子为着丝粒，一个重组子为D14S301(端粒)。这些重组将候选基因座位限制在大约7.2Mb的区域。

A novel dysmorphic syndrome with late-closing fontanels and sutural cataracts (cranio-lenticulo-sutural dysplasia) has been identified in an inbred Saudi Arabian family. The most prominent feature is a failure of closure of the fontanels and sutures; and at birth, the anterior fontanel is large due to open sagittal and metopic sutures. The second major feature is posterior Y-shaped sutural cataracts that are congenital or develop over time. A genome-wide screen was performed using 387 markers at the Center for Inherited Disease Research (CIDR) on 21 DNA samples, and several candidate regions were identified. The genotyping of flanking markers to narrow these candidate regions has been completed as well. Two-point LOD score analysis assuming autosomal recessive inheritance suggested linkage to markers on chromosome 14q13-q21. Model-independent analysis using SIBPAL corroborated linkage to that same area. Haplotype analysis indicated that all affected individuals were homozygous for the interval between markers D14S306-ATA38D06, with two recombinants for D14S556 (centromeric) and one recombinant for D14S301 (telomeric). These recombinations limited the candidate gene locus to a region of approximately 7.2 Mb.