Ha Nguyen Thanh, Chau Hoang Minh, Cung Le Xuan, Thanh Ton Kim, Fujiki Keiko, Murakami Akira, Hiratsuka Yoshimune, Hasegawa Nobuko, Kanai Atsushi
Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
Cornea. 2003 Aug;22(6):508-11. doi: 10.1097/00003226-200308000-00004.
To report the clinical and genetic findings of Vietnamese families affected with macular corneal dystrophy (MCD) in 2 generations.
Two families, including 7 patients and 3 unaffected members, were examined clinically. Blood samples were collected. Fifty normal Vietnamese individuals were used as controls. Genomic DNA was extracted from leukocytes. Analysis of the carbohydrate sulfotransferase (CHST6) gene was performed using polymerase chain reaction and direct sequencing.
The typical form of MCD was recognized in family B, in which sequencing of CHST6 gene revealed an nt 1067-1068ins(GGCCGTG) mutation (frameshift after 125V) homozygously in MCD patients and heterozygously in the unaffected members. Family N also showed clinical features of MCD, moderate in the mother but severe in the affected son. Sequencing revealed a single heterozygous Arg211Gln in the mother, compound heterozygous Arg211Gln+ Gln82Stop in the affected son, and heterozygous Arg211Gln mutation in the unaffected members. The identified mutations in these pedigrees were excluded from normal controls.
The novel frameshift and compound heterozygous mutations might be responsible for MCD in the families studied. The phenotypic variation between affected parents and offspring was unclear. In family N, severe MCD phenotype seen in the affected son may be due the fact that he had an early stop codon mutation (Gln82Stop).
报告两代受黄斑角膜营养不良(MCD)影响的越南家庭的临床和基因研究结果。
对两个家庭进行临床检查,包括7例患者和3名未患病成员。采集血样。选取50名正常越南人作为对照。从白细胞中提取基因组DNA。采用聚合酶链反应和直接测序法对碳水化合物磺基转移酶(CHST6)基因进行分析。
在B家族中识别出典型的MCD形式,其中CHST6基因测序显示,MCD患者中该基因纯合存在nt 1067 - 1068ins(GGCCGTG)突变(125V后移码),未患病成员中为杂合突变。N家族也表现出MCD的临床特征,母亲症状中度,患病儿子症状严重。测序显示母亲存在单一杂合的Arg211Gln突变,患病儿子为复合杂合的Arg211Gln + Gln82Stop突变,未患病成员存在杂合的Arg211Gln突变。这些家系中鉴定出的突变在正常对照中未出现。
新发现的移码突变和复合杂合突变可能是所研究家庭中MCD的病因。患病父母与后代之间的表型差异尚不清楚。在N家族中,患病儿子出现严重的MCD表型可能是由于他存在一个早期终止密码子突变(Gln82Stop)。