Autosomal recessive corneal endothelial dystrophy (CHED2) is associated with mutations in SLC4A11
Autosomal recessive corneal endothelial dystrophy (CHED2) is associated with mutations in SLC4A11
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DOI：
10.1136/jmg.2006.044644
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Kannabiran, Chitra
中科院分区：
文献类型：
--
作者：
Jiao, Xiaodong;Sultana, Afia;Kannabiran, Chitra
目的：为了映射和识别常染色体隐性遗传性先天性遗传性内皮营养不良（CHED 2，OMIM 217700），一种疾病的特点是弥漫性双侧角膜混浊，可能导致视力障碍，需要角膜transplantation.Methods：16个常染色体隐性遗传性CHED家族的成员进行了基因分型的13个微卫星标记在染色体20 p13 -12的CHED 2位点。使用MLINK程序的FASTLINK版本进行两点连锁分析。通过PCR扩增外显子和侧翼区进行突变筛查，然后直接自动测序。结果：连锁和单倍型分析将疾病位点置于2.2 cM（1.3 Mb）的间隔内，两侧为D20 S198和D20 S889，包括SLC 4A 11。使用D20 S117在θ =0时获得的最大检测限评分为11.1。结论：SLC 4A 11基因突变是常染色体隐性遗传性CHED的致病基因。
Objective: To map and identify the gene for autosomal recessive congenital hereditary endothelial dystrophy (CHED2, OMIM 217700), a disorder characterised by diffuse bilateral corneal clouding that may lead to visual impairment and requiring corneal transplantation.Methods: Members of 16 families with autosomal recessive CHED were genotyped for 13 microsatellite markers at the CHED2 locus on chromosome 20p13-12. Two-point linkage analysis was carried out using the FASTLINK version of the MLINK program. Mutation screening was carried out by amplification of exons and flanking regions by polymerase chain reaction, followed by direct automated sequencing.Results: Linkage and haplotype analysis placed the disease locus within a 2.2 cM (1.3 Mb) interval flanked by D20S198 and D20S889, including SLC4A11. The maximum limit of detection score of 11.1 was obtained with D20S117 at theta=0. Sequencing of SLC4A11 showed homozygotic mutations in affected members from 12 of 16 families.Conclusion: These results confirm that mutations in the SLC4A11 gene cause autosomal recessive CHED.