Vazquez C, Antiñolo G, Casals T, Dapena J, Elorz J, Seculi J L, Sirvent J, Cabanas R, Soler C, Estivill X
Cystic Fibrosis Unit, Hospital Infantil de Cruces, Pais Vasco, Spain.
J Med Genet. 1996 Oct;33(10):820-2. doi: 10.1136/jmg.33.10.820.
To study the severity of mutation G85E, located in the first membrane spanning domain of the CFTR gene, we studied the clinical features of 13 Spanish patients with cystic fibrosis (CF) carrying this mutation. G85E accounts for about 1% of Spanish CF alleles. One patient was homozygous G85E/G85E and the rest were compound heterozygotes for G85E and other mutations (delta F508 nine patients, delta I507 two patients, and 712-1G > T one patient). The characteristics of the pooled G85E/any mutation group were compared with those of 30 delta F508 homozygotes. Mean age at diagnosis and percentage of ideal height for age were higher in the G85E/any mutation group (4.2 (SD 4.7) v 2.4 (SD 2.3), p < 0.05, and 102.8 (SD 4.7) v 97.8 (SD 4.1), p < 0.01), both probably related to the greater prevalence of pancreatic sufficiency (70% v 0%, p < 0.01). The G85E homozygote was pancreatic sufficient. Sweat sodium levels were slightly higher, and salt loss related problems more frequent, in the G85E/any group. Two of the G85E patients died of respiratory failure aged 6 and 14 years. Striking discordance in the phenotype was observed in two pairs of sibs, one of them dizygotic twins, suggesting that factors, genetic and environmental, other than CFTR genotype are important in determining CF phenotype.
为研究位于囊性纤维化跨膜传导调节因子（CFTR）基因首个跨膜结构域的G85E突变的严重程度，我们研究了13名携带该突变的西班牙囊性纤维化（CF）患者的临床特征。G85E约占西班牙CF等位基因的1%。1例患者为G85E/G85E纯合子，其余为G85E与其他突变的复合杂合子（9例为ΔF508，2例为ΔI507，1例为712-1G＞T）。将G85E/任何突变组的特征与30例ΔF508纯合子的特征进行比较。G85E/任何突变组的诊断时平均年龄和年龄别理想身高百分比更高（分别为4.2（标准差4.7）对2.4（标准差2.3），p＜0.05；102.8（标准差4.7）对97.8（标准差4.1），p＜0.01），两者可能都与胰腺功能正常的患病率更高有关（70%对0%，p＜0.01）。G85E纯合子胰腺功能正常。G85E/任何突变组的汗液钠水平略高，与盐丢失相关的问题更常见。2例G85E患者分别于6岁和14岁死于呼吸衰竭。在两对同胞中观察到显著的表型不一致，其中一对为异卵双胞胎，这表明除CFTR基因型外，遗传和环境因素在决定CF表型方面也很重要。
