Hemadevi Boomiraj, Veitia Reiner A, Srinivasan Muthiah, Arunkumar Jambulingam, Prajna Namperumalsamy Venkatesh, Lesaffre Corinne, Sundaresan Periasamy
Department of Genetics, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Madurai, India.
Arch Ophthalmol. 2008 May;126(5):700-8. doi: 10.1001/archopht.126.5.700.
To identify Solute Carrier family 4 (sodium borate cotransporter) member 11 (SLC4A11) gene mutations associated with autosomal recessive congenital hereditary endothelial dystrophy (CHED2).
DNA extraction from blood, polymerase chain reaction amplification, and direct sequencing of all the exons of the SLC4A11 gene were performed for 26 affected members of 20 unrelated families with CHED2.
Of 10 mutations observed, 6 were novel, 1 of which involves a complete deletion of exon 6, identified for the first time, to our knowledge, in SLC4A11. The mutations cosegregated with the disease phenotype and were absent in 200 ethnically matched control chromosomes analyzed.
This study increases the number of SLC4A11 gene mutations and confirms the role of this gene in causing CHED2. Clinical examination did not reveal any considerable variability in disease expressivity in patients carrying SLC4A11 mutations. Extensive linkage analysis may reveal the modifier genes involved in causing CHED2 in the SLC4A11 mutations unidentified in 9 families.
In India, there is a high frequency of CHED2, possibly related to consanguineous marriages. Counseling could be provided to explain the drawbacks of consanguineous marriages to assist in reducing this devastating disorder.
鉴定与常染色体隐性先天性遗传性内皮营养不良（CHED2）相关的溶质载体家族4（硼酸钠共转运体）成员11（SLC4A11）基因突变。
对20个不相关的CHED2家族的26名患病成员进行血液DNA提取、聚合酶链反应扩增以及SLC4A11基因所有外显子的直接测序。
在观察到的10个突变中，6个是新的，其中1个涉及外显子6的完全缺失，据我们所知，这在SLC4A11中是首次发现。这些突变与疾病表型共分离，在分析的200条种族匹配的对照染色体中未出现。
本研究增加了SLC4A11基因突变的数量，并证实了该基因在导致CHED2中的作用。临床检查未发现携带SLC4A11突变的患者在疾病表达上有任何显著差异。广泛的连锁分析可能揭示在9个家族中未鉴定出的SLC4A11突变中导致CHED2的修饰基因。
在印度，CHED2的发病率很高，可能与近亲结婚有关。可以提供咨询，解释近亲结婚的弊端，以帮助减少这种毁灭性疾病。
