Guevara-Fujita Maria Luisa, Perez-Grossmann Rodolfo A, Estrada-Cuzcano Alejandro, Pawar Hemant, Vargas Enrique, Richards Julia E, Fujita Ricardo
Centro de Genética y Biología Molecular, Facultad de Medicina, Universidad de San Martín de Porres, Instituto de Glaucoma y Catarata, Lima, Peru.
J Glaucoma. 2008 Jan-Feb;17(1):67-72. doi: 10.1097/IJG.0b013e318133fc5b.
To search for MYOC mutations in Peruvian primary open angle glaucoma (POAG) families.
Two patients from each of the 11 POAG Peruvian families were screened for sequence variants in MYOC coding exons by conformational sensitive gel electrophoresis and sequencing was performed on the samples indicating probable sequence changes.
We detected 2 families bearing distortions of conformational sensitive gel electrophoresis indicating mutations. Sequencing of these samples revealed coding sequence changes. A native Andean descent family presented with a MYOC mutation, Asn480Lys (C-->G at nucleotide 1440). This is different from the previously reported C-->A change at nucleotide 1440 that causes Asn480Lys in 2 unrelated French and Dutch families with glaucoma of variable expressivity, and indicates a third independent event. A second family of admixed origin showed the presence of the known Arg76Lys polymorphism.
In the study of MYOC variants in 11 POAG Peruvian families, we have found a family of ethnically admixed origin with polymorphism Arg76Lys and a family of Andean descent bearing a third event of the Asn480Lys, the MYOC mutation that has been reported in the highest number of POAG patients (>80 cases). Analysis of this family could contribute with information about disease manifestation, progression, and treatment response in the context of a distinct genetic background and also climatic, altitude, and socioeconomical conditions.
在秘鲁原发性开角型青光眼（POAG）家族中寻找MYOC基因突变。
对11个秘鲁POAG家族中的每个家族的两名患者进行筛查，通过构象敏感凝胶电泳检测MYOC编码外显子中的序列变异，并对显示可能序列变化的样本进行测序。
我们检测到2个家族的构象敏感凝胶电泳出现畸变，表明存在突变。对这些样本进行测序揭示了编码序列的变化。一个安第斯血统的家族出现了MYOC突变，即Asn480Lys（核苷酸1440处C→G）。这与之前报道的核苷酸1440处C→A的变化不同，后者在2个患有不同表达性青光眼的不相关法国和荷兰家族中导致Asn480Lys，表明这是第三个独立事件。另一个混合血统的家族显示存在已知的Arg76Lys多态性。
在对11个秘鲁POAG家族的MYOC变异研究中，我们发现了一个具有Arg76Lys多态性的混合血统家族，以及一个安第斯血统的家族，该家族出现了Asn480Lys这一第三个事件，Asn480Lys是在POAG患者中报道数量最多（>80例）的MYOC突变。对这个家族的分析可以在独特的遗传背景以及气候、海拔和社会经济条件的背景下，为疾病表现、进展和治疗反应提供信息。
