Paliwal Preeti, Sharma Arundhati, Tandon Radhika, Sharma Namrata, Titiyal Jeewan S, Sen Seema, Nag Tapas C, Vajpayee Rasik B
Laboratory of Cyto-Molecular Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Mol Vis. 2010 Dec 31;16:2955-63.
To identify the solute carrier family 4 (sodium borate cotransporter) member 11 (SLC4A11) mutation spectrum and to perform genotype-phenotype correlations in autosomal recessive Congenital Hereditary Endothelial Dystrophy (CHED2) in North Indian patients.
Twenty-five patients from twenty families clinically diagnosed with autosomal recessive CHED2 were recruited for the study. Clinical parameters such as age at onset, presentation, and pre- and post-operative visual acuities were recorded. Corneal buttons of patients undergoing keratoplasty were analyzed for histopathologic and ultrastructural confirmation. All the affected individuals and 50 unrelated population matched normal controls were screened for underlying sequence changes. Genomic DNA was isolated from peripheral blood samples and all the exons and the 5'-upstream region of the SLC4A11 gene were screened for mutations by direct DNA sequencing.
A high degree of consanguinity (9 out of 20 families) was noted. Corneal haze was reported to be present since birth or shortly thereafter in all affected patients. Histology and electron microscopy studies revealed increased thickness of Descemet's membrane, especially of the non-banded zone. Molecular studies revealed one novel homozygous in-frame deletion mutation in two affected siblings from one family and three other previously reported homozygous mutations in 12 patients from 9 families. Mutations were not identified in 11 patients from 11 families. High interfamilial and intrafamilial phenotypic variability was seen among the cohort of patients.
This is the first report on the mutation spectrum and genotype-phenotype correlation in CHED2 patients from North India. The present study detected one novel and three reported changes, adding to the repertoire of mutations in SLC4A11, and recorded a high degree of genetic heterogeneity in CHED2.
确定溶质载体家族4（硼酸钠共转运体）成员11（SLC4A11）的突变谱，并对北印度常染色体隐性先天性遗传性内皮营养不良（CHED2）患者进行基因型-表型相关性分析。
招募了来自20个家庭的25例临床诊断为常染色体隐性CHED2的患者进行研究。记录了诸如发病年龄、临床表现以及手术前后视力等临床参数。对接受角膜移植手术患者的角膜组织块进行组织病理学和超微结构分析以进行确诊。对所有患病个体和50名无亲缘关系的匹配正常对照进行潜在序列变化筛查。从外周血样本中提取基因组DNA，通过直接DNA测序对SLC4A11基因的所有外显子和5'-上游区域进行突变筛查。
发现高度近亲结婚情况（20个家庭中有9个）。据报道，所有患病患者自出生时或出生后不久即存在角膜混浊。组织学和电子显微镜研究显示Descemet膜厚度增加，尤其是无带区。分子研究发现一个家庭的两名患病同胞中有一个新的纯合框内缺失突变，以及9个家庭的12名患者中有另外三个先前报道的纯合突变。11个家庭的11名患者未发现突变。在患者队列中观察到高度的家族间和家族内表型变异性。
这是关于北印度CHED2患者突变谱和基因型-表型相关性的首次报告。本研究检测到一个新的和三个已报道的变化，增加了SLC4A11的突变种类，并记录了CHED2中高度的遗传异质性。
