先天性单纯性小眼球症的一个新基因座定位于 17p12-q12。

A novel locus for congenital simple microphthalmia family mapping to 17p12-q12.

机构信息

The State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.

出版信息

Invest Ophthalmol Vis Sci. 2011 May 18;52(6):3425-9. doi: 10.1167/iovs.10-6747.

DOI:10.1167/iovs.10-6747

PMID:21345985

Abstract

PURPOSE

To investigate the etiology in a family with autosomal-dominant congenital simple microphthalmia of Chinese origin.

METHODS

A whole-genome scan was performed by using 382 microsatellite DNA markers after the exclusion of reported candidates linked to microphthalmia. Additional fluorescent markers were genotyped for fine mapping. To find out the novel predisposing gene, 14 candidate genes including CRYBA1 and NCOR1 were selected to screen for the mutation by the PCR direct-sequencing method. Genome-wide single-nucleotide polymorphism (SNP) genotyping was performed to find out the pathogenetic copy number variation, as well.

RESULTS

The most statistically significant linkage results were obtained at D17S1824 (maximum LOD score, 4.97, at recombination fraction 0.00). Haplotype analyses supported the location of the disease-causing gene to a 21.57-cM interval between loci D17S900 and D17S1872 of chromosome 17, region p12-q12. However, no mutation or CNV (copy number variation) was identified to be responsible for the microphthalmia phenotype of this pedigree.

CONCLUSIONS

A novel suggestive linkage locus for congenital microphthalmia was detected in a Chinese family. This linkage region provides a target for susceptibility gene identification.

摘要

目的

研究一个常染色体显性遗传的先天性单纯性小眼球症的家系的病因。

方法

在排除与小眼球症相关的已报道候选基因后，通过使用 382 个微卫星 DNA 标记进行全基因组扫描。为了进行精细定位，还对额外的荧光标记进行了基因分型。为了寻找新的致病基因，选择了 14 个候选基因，包括 CRYBA1 和 NCOR1，通过 PCR 直接测序法筛选突变。还进行了全基因组单核苷酸多态性（SNP）基因分型，以发现致病的拷贝数变异。

结果

在 D17S1824 处获得了最显著的连锁结果（最大 LOD 评分 4.97，重组分数为 0.00）。单倍型分析支持致病基因位于 17 号染色体 D17S900 和 D17S1872 之间的 21.57-cM 区间，即染色体 17 的 p12-q12 区域。然而，未发现突变或 CNV（拷贝数变异）可导致该家系的小眼球表型。