一个反复出现的深内含子剪接 CF 突变强调了在临床实践中进行 mRNA 研究的重要性。
A recurrent deep-intronic splicing CF mutation emphasizes the importance of mRNA studies in clinical practice.
机构信息
APHP, Groupe hospitalier Henri Mondor, Service de Biochimie-Génétique, Créteil, F-94010, France.
出版信息
J Cyst Fibros. 2011 Dec;10(6):479-82. doi: 10.1016/j.jcf.2011.06.011. Epub 2011 Jul 23.
BACKGROUND
The identification by CFTR mRNA studies of a new deep-intronic splicing mutation, c.870-1113_1110delGAAT, in one patient of our series with mild CF symptoms and in three CF patients of an Italian study, led us to evaluate the mutation frequency and phenotype/genotype correlations.
METHODS
266 patients with CF and related disorders and having at least one undetected mutation, were tested at the gDNA level in three French reference laboratories.
RESULTS
In total, the mutation was found in 13 unrelated patients (5% of those already carrying a mutation) plus 4 siblings, including one homozygote and 12 heterozygotes having a severe CF mutation. The sweat test was positive in 10/14 documented cases, the diagnosis was delayed after 20 years in 9/15 and pancreatic insufficiency was present in 5/16.
CONCLUSION
c.870-1113_1110delGAAT should be considered as CF-causing with phenotype variability and overall delayed diagnosis. Its frequency highlights the potential of mRNA studies.
背景
通过 CFTR mRNA 研究鉴定出一个新的深内含子剪接突变 c.870-1113_1110delGAAT，在我们系列中一名具有轻度 CF 症状的患者和意大利研究的三名 CF 患者中均存在该突变，这促使我们评估该突变的频率以及表型/基因型相关性。
方法
在三个法国参考实验室，对 266 名具有 CF 和相关疾病且至少存在一个未检测到的突变的患者进行 gDNA 水平检测。
结果
该突变共在 13 名无关联患者（已携带突变患者的 5%）及 4 名同胞中发现，包括 1 名纯合子和 12 名携带严重 CF 突变的杂合子。在 14 例有记录的病例中，汗液测试阳性，15 例中有 9 例诊断延迟至 20 年后，16 例中有 5 例存在胰腺功能不全。
结论
c.870-1113_1110delGAAT 应被视为 CF 致病突变，具有表型变异性和整体延迟诊断。其频率突显了 mRNA 研究的潜力。
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