Sultana Afia, Garg Prashant, Ramamurthy Balasubramanya, Vemuganti Geeta K, Kannabiran Chitra
Kallam Anji Reddy Molecular Genetics Laboratory, L.V. Prasad Eye Institute, Hyderabad, India.
Mol Vis. 2007 Jul 26;13:1327-32.
Autosomal recessive congenital hereditary endothelial dystrophy (AR-CHED or CHED2) is a bilateral corneal disorder manifesting at birth or in early childhood. CHED2 is caused by mutations in the sodium bicarbonate transporter-like solute carrier family 4 member 11 (SLC4A11) gene on chromosome 20p13. We screened 42 unrelated families with CHED2 in order to establish the spectrum of mutations in SLC4A11 and to look for genotype-phenotype correlations.
Forty-two families (49 affected and 73 unaffected members) with recessive CHED were recruited according to predefined diagnostic criteria. Clinical data including age at onset and presentation, pre- and post-operative visual acuities, and presence of nystagmus were taken from patient records. Histopathologic parameters such as corneal thickness, Descemet membrane thickness, and endothelial cell counts were assessed on corneal sections. DNA from patients was screened for sequence changes by polymerase chain reaction (PCR)-amplification of coding regions of SLC4A11 and single strand conformation polymorphism analysis followed by sequencing. Sequence changes found were tested in 50 unrelated normal controls.
Twenty-seven different mutations were identified in 35 unrelated families, 19 of which were not previously reported. The mutations identified consisted of 13 missense, 5 nonsense, 7 deletions, 1 complex (deletion plus insertion) mutation, and 1 splice site mutation. Both mutant alleles were identified in 33 families and only one mutant allele in two families. No correlations were evident between clinical or histopathologic parameters and SLC4A11 mutations.
These data add to the mutational repertoire of SLC4A11 and establish the high degree of mutational heterogeneity in autosomal recessive CHED.
常染色体隐性先天性遗传性内皮营养不良（AR-CHED或CHED2）是一种在出生时或儿童早期出现的双侧角膜疾病。CHED2由位于20号染色体p13上的碳酸氢钠转运体样溶质载体家族4成员11（SLC4A11）基因突变引起。我们对42个无关的CHED2家族进行了筛查，以确定SLC4A11基因突变谱，并寻找基因型与表型的相关性。
根据预先定义的诊断标准招募了42个隐性CHED家族（49名患者和73名未患病成员）。临床数据包括发病年龄和表现、手术前后视力以及眼球震颤情况，均取自患者记录。在角膜切片上评估组织病理学参数，如角膜厚度、Descemet膜厚度和内皮细胞计数。通过聚合酶链反应（PCR）扩增SLC4A11编码区并进行单链构象多态性分析，随后进行测序，筛查患者的DNA序列变化。在50名无关的正常对照中检测发现的序列变化。
在35个无关家族中鉴定出27种不同的突变，其中19种此前未曾报道。鉴定出的突变包括13种错义突变、5种无义突变、7种缺失突变、1种复合（缺失加插入）突变和1种剪接位点突变。在33个家族中鉴定出两个突变等位基因，在两个家族中仅鉴定出一个突变等位基因。临床或组织病理学参数与SLC4A11突变之间未发现明显相关性。
这些数据增加了SLC4A11的突变库，并证实了常染色体隐性CHED中高度的突变异质性。
