A novel homozygous complex deletion in CFTR caused cystic fibrosis in a Chinese patient

Cystic fibrosis (CF) is the most frequent lethal genetic disorder among Caucasians, but is considered to be a very rare disease in Chinese population. Here, we present an 11-year-old Chinese CF patient with disseminated bronchiectasis and salty sweat, for whom exon sequencing followed by multiplex ligation-dependent probe amplification analysis of the CFTR gene was applied for mutation screening. A homozygous deletion involving exon 20 of CFTR was observed in the patient's genome. Molecular characterization of the breakpoints indicated that both alleles of this locus had an identical novel complex rearrangement (c.3140-454_c.3367+249del931ins13, p.R1048_G1123del), leading to an in-frame removal of 76 amino acid residues in the second transmembrane domains of the CFTR protein. Although a same haplotype containing this complex rearrangement was observed on both of the maternal and paternal alleles, the parents denied any blood relationship as far as they know. Genome-wide homozygosity mapping was performed through SNP microarray and only a single homozygous interval of -14.1 Mb at chromosome 7 containing the CFTR gene was observed, indicating the possible origin of the deletion from a common ancestor many generations ago. This study expands the mutation spectrum of CFTR in patients of Chinese origin and further emphasizes the necessity of MLPA analysis in mutation screening for CF patients.