囊性纤维化跨膜电导调节因子基因突变的基因型模式：来自沙特阿拉伯的回顾性描述性研究。
Genotype patterns for mutations of the cystic fibrosis transmembrane conductance regulator gene: a retrospective descriptive study from Saudi Arabia.
机构信息
From the Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
From the Department of Medicine, Al Faisal University, Riyadh, Saudi Arabia.
出版信息
Ann Saudi Med. 2020 Jan-Feb;40(1):15-24. doi: 10.5144/0256-4947.2020.15. Epub 2020 Feb 6.
BACKGROUND
Cystic fibrosis (CF) occurs in populations in Saudi Arabia and the Gulf area. Approximately 2000 known variants have been identified for the CF transmembrane conductance regulator (CTFR) gene. Screening for ten of the most common variants can detect 80% of alleles.
OBJECTIVE
Determine the pattern of CFTR variants in the CF population of Saudi Arabia.
DESIGN
A retrospective, descriptive.
SETTING
Tertiary care center.
PATIENTS AND METHODS
We examined the medical records of 396 confirmed CF patients of all age groups that were positive for a CFTR variant from the period of 1 January 1998 to 1 December 2017.
MAIN OUTCOME MEASURES
Zygosity, morbidity and mortality patterns of different types of CFTR variants.
SAMPLE SIZE
312 families that included 396 patients.
RESULTS
Of 48 variants identified, 6 were novel, having not been described in the medical literature. A homozygous state was found in 283 families (90.7%) and compound heterozygosity in 23 (7.4%). Six families were heterozygous (1.9%). Median age (interquartile range) was 10.2 months (4.4 months to 5.7 years) at diagnosis and 9.7 (5.4-16.5) years at follow up. Of 396 patients, 378 patients (95.5%) survived and 18 (4.5%) died. The ten most common variants identified in descending frequency were: p.Gly473GlufsX54 in 98 alleles (16%), p.Ile1234Val in 66 alleles (11%), F508del in 64 alleles (11%), 711+1G>T in 62 alleles (10%), 3120+1G>A in 62 alleles (11%), p.His139Leuin 38 alleles (6.4%), p.Gln637Hisfs in 30 alleles (5.2%), p.Ser549Arg in 27 alleles (4.5%), p.Asn1303Lys in 14 alleles (2.3%), delExon19-21in 10 alleles (1.6%). This analysis identified 79.2% of our CFTR variants.
CONCLUSION
CFTR mutational patterns in our CF population are characterized by a high allelic heterogeneity. The high prevalence of homozygous variants reflects the high level of consanguinity between parents.
LIMITATIONS
Our CFTR screening reflected only about 80% of CF patients in Saudi Arabia.
CONFLICT OF INTEREST
None.
背景
囊性纤维化（CF）发生在沙特阿拉伯和海湾地区的人群中。已经鉴定出 CF 跨膜电导调节剂（CTFR）基因的大约 2000 个已知变体。对十种最常见变体进行筛查可以检测到 80%的等位基因。
目的
确定沙特阿拉伯 CF 人群中 CFTR 变体的模式。
设计
回顾性，描述性。
地点
三级护理中心。
患者和方法
我们检查了 1998 年 1 月 1 日至 2017 年 12 月 1 日期间，所有年龄组的 396 名 CFTR 变体阳性的确诊 CF 患者的医疗记录。
主要观察指标
不同类型 CFTR 变体的同合子状态、发病率和死亡率模式。
样本量
包括 396 名患者的 312 个家庭。
结果
在鉴定的 48 种变体中，有 6 种是新的，尚未在医学文献中描述。283 个家庭（90.7%）为纯合状态，23 个家庭（7.4%）为复合杂合状态。6 个家庭为杂合子（1.9%）。诊断时的中位年龄（四分位间距）为 10.2 个月（4.4 个月至 5.7 岁），随访时为 9.7（5.4-16.5）岁。396 名患者中，378 名（95.5%）存活，18 名（4.5%）死亡。按频率降序排列的前 10 种最常见变体是：p.Gly473GlufsX54 98 个等位基因（16%），p.Ile1234Val 66 个等位基因（11%），F508del 64 个等位基因（11%），711+1G>T 62 个等位基因（10%），3120+1G>A 62 个等位基因（11%），p.His139Leu 38 个等位基因（6.4%），p.Gln637Hisfs 30 个等位基因（5.2%），p.Ser549Arg 27 个等位基因（4.5%），p.Asn1303Lys 14 个等位基因（2.3%），delExon19-21 10 个等位基因（1.6%）。该分析确定了我们 CFTR 变体的 79.2%。
结论
我们 CF 人群中 CFTR 突变模式的特点是等位基因高度异质性。纯合变体的高患病率反映了父母之间近亲繁殖的高水平。
局限性
我们的 CFTR 筛查仅反映了沙特阿拉伯约 80%的 CF 患者。
利益冲突
无。
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