Chen Yuhong, Jiang Deke, Wan Bo, Yu Long, Sun Xinghuai
State Key Laboratory of Genetic Engineering, Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
Mol Vis. 2006 Apr 17;12:360-6.
To provide genetic counseling and presymptomatic diagnosis to family members by investigating the genetic cause of a large primary juvenile open angle glaucoma (JOAG) pedigree with an autosomal dominant pattern.
Ocular examinations were performed on all members of the pedigree in order to determine their disease status. Subjects were labeled as affected individuals, unaffected individuals, and suspects. Genomic DNA was extracted from the peripheral blood of the family members. Three exons of MYOC, 12 coding exons of OPTN, and two coding exons of CYP1B1 were amplified by polymerase chain reaction (PCR). Direct DNA sequencing was used to identify mutations in MYOC, OPTN, and CYP1B1. Presymptomatic diagnoses were made for the consulters based on the results of both clinical examination and genetic analysis.
One heterozygous mutation in the MYOC gene was identified in all patients of the pedigree. It was a cytosine to thymine transition at nucleotide 1,109, which corresponded to an amino acid residue change from proline to leucine at codon 370. The Pro370Leu mutation correlated with a severe JOAG phenotype as previously reported. Two adolescents, who were labeled as suspects, were detected to carry the same mutation and thus had a high risk of developing glaucoma. Close follow-up at regular intervals was recommended. In addition, no pathogenic mutations of OPTN and CYP1B1 were detected.
The Pro370Leu mutation of the MYOC gene contributed to JOAG in this pedigree. Early onset, rapid development, poor response to medicine and high penetrance are characteristics of this mutation. Genetic analysis is valuable for providing genetic counseling and presymptomatic diagnosis to members in typical autosomal inheritance pedigrees with JOAG.
通过调查一个具有常染色体显性遗传模式的大型原发性青少年开角型青光眼（JOAG）家系的遗传病因，为家庭成员提供遗传咨询和症状前诊断。
对该家系的所有成员进行眼科检查，以确定他们的疾病状态。将受试者标记为患病个体、未患病个体和疑似个体。从家庭成员的外周血中提取基因组DNA。通过聚合酶链反应（PCR）扩增MYOC的3个外显子、OPTN的12个编码外显子和CYP1B1的2个编码外显子。采用直接DNA测序法鉴定MYOC、OPTN和CYP1B1中的突变。根据临床检查和遗传分析结果，为咨询者进行症状前诊断。
在该家系的所有患者中均鉴定出MYOC基因中的一个杂合突变。它是核苷酸1109处的胞嘧啶到胸腺嘧啶的转变，对应于密码子370处脯氨酸到亮氨酸的氨基酸残基变化。如先前报道，Pro370Leu突变与严重的JOAG表型相关。两名被标记为疑似个体的青少年被检测出携带相同的突变，因此患青光眼的风险很高。建议定期密切随访。此外，未检测到OPTN和CYP1B1的致病突变。
MYOC基因的Pro370Leu突变导致了该家系中的JOAG。该突变的特征是发病早、发展快、药物反应差和外显率高。遗传分析对于为具有JOAG的典型常染色体遗传家系中的成员提供遗传咨询和症状前诊断具有重要价值。
