Shah Uzma, Frossard Phillipe, Moatter Tariq
Harvard Medical School Dubai Center, Dubai, UAE.
Trop Med Int Health. 2009 May;14(5):542-5. doi: 10.1111/j.1365-3156.2009.02253.x.
Cystic fibrosis is frequently missed in the Pakistani population due to lack of appropriate diagnostic tools. Thus our aim was to define unknown disease-causing mutations to help create suitable diagnostic tests and improve understanding of what appears to be an aggressive and under-diagnosed disease in this population.
Patients with elevated sweat chloride values and clinically suspected CF were recruited from Aga Khan University, Pakistan. Mutations DF508, S549R, S549N, Y569D, 296 + 12(T>C), G553X, G551D and G551X were screened for by allele specific polymerase chain reactions. CFTR exons 10, 11 and 12 were sequenced by direct DNA sequencing.
Of 150 patients tested by PCR, 26 (17.3%) were positive for DeltaF508. One patient was a F508/S549N compound heterozygote. Eighty-three of 87 patients sequenced for mutations in exon 10 were normal; 42/43 for exon 11 and 29 for exon 12 were normal.
This first step in defining mutations involved in Pakistani CF suggests that DeltaF508 is uncommon and S549 was the only additional mutation identified in CFTR exons 10, 11 and 12. Identification of the remaining mutations and their frequency is required to design appropriate tests and improve understanding and management of the disease.
由于缺乏合适的诊断工具，巴基斯坦人群中囊性纤维化常被漏诊。因此，我们的目的是确定未知的致病突变，以帮助创建合适的诊断测试，并增进对这种在该人群中似乎具有侵袭性且诊断不足的疾病的了解。
从巴基斯坦阿迦汗大学招募汗液氯化物值升高且临床怀疑患有囊性纤维化的患者。通过等位基因特异性聚合酶链反应筛查DF508、S549R、S549N、Y569D、296 + 12(T>C)、G553X、G551D和G551X突变。通过直接DNA测序对CFTR外显子10、11和12进行测序。
在150例接受PCR检测的患者中，26例（17.3%）DeltaF508呈阳性。1例患者为F508/S549N复合杂合子。在87例对第10外显子突变进行测序的患者中，83例正常；第11外显子42/43例正常，第12外显子29例正常。
确定巴基斯坦囊性纤维化相关突变的这第一步表明，DeltaF508并不常见，S549是在CFTR外显子10、11和12中唯一鉴定出的其他突变。需要确定其余突变及其频率，以设计合适的检测方法，并增进对该疾病的了解和管理。
