Prenatal Detection by Real-Time Quantitative PCR and Characterization of a New CFTR Deletion, 3600+15kbdel5.3kb (or CFTRdele19)

Abstract

Cystic fibrosis (CF; MIM No. 219700), the most common autosomal recessive disease in Caucasians (1), is caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR; MIM No. 602421) (2). The disease may be revealed by fetal bowel hyperechogenicity during routine ultrasonography in the second trimester of pregnancy, even when there is no family history of CF. However, fetal bowel hyperechogenicity is not specific for CF: when found at this stage of pregnancy, it corresponds to CF in 2–20% of cases (1)(3)(4)(5). Diagnostic investigations are based on screening for CF-causing mutations, fetal karyotyping, and screening for infections. Normal intestinal enzyme activities in amniotic fluid before 18 weeks of gestation reasonably rules out CF (6). However, most women are referred after this time, and it is necessary to screen for CF mutations in the parents and, if possible, fetus. To date, almost 900 mutations have been described throughout the CFTR gene, but very few deletions have been identified (7). Indeed, large deletions are not routinely screened for, given their rarity and the lack of suitable diagnostic tools. Conventional PCR-based methods usually detect deletions only when they are present in the homozygous state. As a result, the frequency of CFTR deletions is underestimated. Two relatively frequent large deletions have recently been described: 3120+1kbdel8.6kb was found in 13% of CF chromosomes in Israeli-Arab patients (8), and CFTRdele2,3 accounts for 1–6.4% of CF chromosomes in Slavic populations (9). A couple was referred to our laboratory for fetal hyperechogenic bowel diagnosed during a routine ultrasound scan at 20 weeks of gestation. The couple, who were first cousins of Turkish extraction, had no family history of CF. Diagnostic investigations were requested after genetic counseling, with the couple’s informed consent. The fetal karyotype (amniotic cells) was normal, as …