VanderVeen Deborah K, Andrews Caroline, Nihalani Bharti R, Engle Elizabeth C
Department of Ophthalmology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
Mol Vis. 2011;17:3333-8. Epub 2011 Dec 20.
To describe phenotypic characteristics of two pedigrees manifesting early onset crystalline cataract with mutations in the γD-crystallin gene (CRYGD).
A detailed medical history was obtained from two Caucasian pedigrees manifesting autosomal dominant congenital cataracts. Genomic DNA was extracted from saliva (DNA Genotek). Single Nucleotide Polymorphism (SNP) based genome analysis of the larger pedigree revealed linkage to an 8.2 MB region on chromosome 2q33-q35 which encompassed the crystallin-gamma gene cluster (CRYG). Exons and flanking introns of CRYGA, CRYGB, CRYGC and CRYGD were amplified and sequenced to identify disease-causing mutations.
A morphologically unique cataract with extensive refractile "crystals" scattered throughout the nucleus and perinuclear cortex was found in the probands from both pedigrees. A heterozygous C→A mutation was identified at position 109 of the coding sequence (R36S of the processed protein) in exon 2 of CRYGD and this missense mutation was found to cosegregate with the disease in the larger family; this mutation was then identified in affected individuals of pedigree 2 as well.
The heterozygous 109C→A CRYGD missense mutation is associated with a distinct crystalline cataract in two US Caucasian pedigrees. This confirms crystalline cataract formation with this mutation, as previously reported in sporadic childhood case from the Czech Republic and in members of a Chinese family.
描述两个家系的表型特征，这两个家系表现为早发性晶状体性白内障且γD-晶状体蛋白基因（CRYGD）存在突变。
从两个表现为常染色体显性先天性白内障的白种人家系中获取详细病史。从唾液（DNA Genotek）中提取基因组DNA。对较大家系进行基于单核苷酸多态性（SNP）的基因组分析，结果显示与2号染色体q33-q35上一个8.2MB的区域存在连锁，该区域包含晶状体蛋白γ基因簇（CRYG）。对CRYGA、CRYGB、CRYGC和CRYGD的外显子及侧翼内含子进行扩增和测序，以确定致病突变。
在两个家系的先证者中均发现了一种形态独特的白内障，其核内和核周皮质中散在分布着大量有折光性的“晶体”。在CRYGD外显子2的编码序列第109位发现了一个杂合的C→A突变（加工后蛋白质的R36S），并且在较大的家系中发现该错义突变与疾病共分离；随后在2号家系的患病个体中也发现了此突变。
杂合的109C→A CRYGD错义突变与两个美籍白种人家系中一种独特的晶状体性白内障相关。这证实了此前在捷克共和国的散发性儿童病例以及一个中国家系成员中报道的该突变可导致晶状体性白内障的形成。
