Gonzalez-Rodriguez Johanna, Ramirez-Miranda Arturo, Hernandez-Da Mota Sergio E, Zenteno Juan C
Department of Genetics-Research Unit, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
Graefes Arch Clin Exp Ophthalmol. 2014 Aug;252(8):1267-72. doi: 10.1007/s00417-014-2648-9. Epub 2014 May 7.
The purpose of our study was to describe the results of molecular screening of TGFBI, CHST6, and GSN genes in a group of Mexican patients with different stromal corneal dystrophies (CD).
A total of 16 CD Mexican patients pertaining to nine different pedigrees were subjected to a complete ophthalmological investigation. A clinical diagnosis of lattice CD was performed in 10 patients from five pedigrees. Three patients from two pedigrees were diagnosed with granular CD type 2, two patients with unrelated probands had Finnish-type corneal amyloidosis, and one patient had macular CD. Genetic analysis included DNA isolation from blood leukocytes and polymerase chain reaction (PCR) amplification and direct nucleotide sequencing of TGFBI, CHST6, and GSN genes.
Seven lattice CD patients from four unrelated families had an identical p.H626R mutation in TGFBI, three patients from a single lattice CD family carried a p.R124C substitution in TGFBI, and a granular type 2 CD pedigree was demonstrated to carry a heterozygous TGFBI p.M619K substitution. A patient having Finnish-type corneal amyloidosis had a p.D187N mutation in GSN. Finally, molecular analysis of CHST6 in a patient with macular CD disclosed the presence of a homozygous p.Y110C change.
This study improves the knowledge of the genetic features of Mexican patients with corneal stromal dystrophies by identifying mutations in the TGFBI, CHST6, and GSN genes. Genetic screening of larger samples of patients from distinct ethnic groups would be of great importance for a better understanding of the mutational spectrum of stromal CD.
我们研究的目的是描述在一组患有不同角膜基质营养不良（CD）的墨西哥患者中，对TGFBI、CHST6和GSN基因进行分子筛查的结果。
对来自9个不同家系的16例患有角膜基质营养不良的墨西哥患者进行了全面的眼科检查。对来自5个家系的10例患者进行了格子状角膜营养不良的临床诊断。来自2个家系的3例患者被诊断为颗粒状角膜营养不良2型，2例无关先证者患有芬兰型角膜淀粉样变性，1例患者患有黄斑状角膜营养不良。基因分析包括从血液白细胞中分离DNA，以及对TGFBI、CHST6和GSN基因进行聚合酶链反应（PCR）扩增和直接核苷酸测序。
来自4个无关家族的7例格子状角膜营养不良患者在TGFBI基因中存在相同的p.H626R突变，来自单个格子状角膜营养不良家族的3例患者在TGFBI基因中携带p.R124C替代突变，一个颗粒状2型角膜营养不良家系被证明携带杂合的TGFBI p.M619K替代突变。1例患有芬兰型角膜淀粉样变性的患者在GSN基因中有p.D187N突变。最后，对1例黄斑状角膜营养不良患者的CHST6进行分子分析，发现存在纯合的p.Y110C改变。
本研究通过鉴定TGFBI、CHST6和GSN基因中的突变，提高了对墨西哥角膜基质营养不良患者遗传特征的认识。对来自不同种族的更大样本患者进行基因筛查，对于更好地了解角膜基质营养不良的突变谱具有重要意义。
