Department of Medical Sciences, University of Trieste, Trieste, Italy.
Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy.
Mol Genet Genomic Med. 2022 Jun;10(6):e1926. doi: 10.1002/mgg3.1926. Epub 2022 Mar 29.
Despite consolidated guidelines, the clinical diagnosis and prognosis of cystic fibrosis (CF) is still challenging mainly because of the extensive phenotypic heterogeneity and the high number of CFTR variants, including their combinations as complex alleles.
We report a family with a complicated syndromic phenotype, which led to the suspicion not only of CF, but of a dominantly inherited skeletal dysplasia (SD). Whereas the molecular basis of the SD was not clarified, segregation analysis was central to make a correct molecular diagnosis of CF, as it allowed to identify three CFTR variants encompassing two known maternal mutations and a novel paternal microdeletion.
This case well illustrates possible pitfalls in the clinical and molecular diagnosis of CF; presence of complex phenotypes deflecting clinicians from appropriate CF recognition, and/or identification of two mutations assumed to be in trans but with an unconfirmed status, which underline the importance of an in-depth molecular CFTR analysis.
尽管有明确的指南，囊性纤维化（CF）的临床诊断和预后仍然具有挑战性，主要是因为其表型异质性广泛，以及 CFTR 变体数量众多，包括它们作为复杂等位基因的组合。
我们报告了一个具有复杂综合征表型的家族，这不仅引起了 CF 的怀疑，还引起了显性遗传骨骼发育不良（SD）的怀疑。虽然 SD 的分子基础尚未阐明，但分离分析对于 CF 的正确分子诊断至关重要，因为它允许识别三个 CFTR 变体，包括两个已知的母系突变和一个新的父系微缺失。
该病例很好地说明了 CF 临床和分子诊断中可能出现的陷阱；存在复杂的表型使临床医生无法正确识别 CF，以及/或识别两个假定为反式但状态未经证实的突变，这突显了深入进行 CFTR 分子分析的重要性。
