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Arch Hellen Med, 23(5), September-October 2006, 455-472


Screening for cystic fibrosis mutations:
Methods for molecular diagnosis, prenatal diagnosis and carrier identification
amongst high-risk individuals - the Greek experience

Department of Medical Genetics, "St. Sophia" Children's Hospital, University of Athens, Athens, Greece

OBJECTIVE Cystic fibrosis (CF) is a severe autosomal recessive genetic disease, affecting 1 in 2,500 Caucasians, with 4% being asymptomatic carriers. The aim of this study was to characterize the spectrum of CF mutations in the Greek population with the purpose of initiating a prevention program for the identification of carriers among high risk individuals, including males with sterility, and offering prenatal diagnosis (P).

METHOD Mutation identification with the use of denaturing gradient gel electrophoresis (DGGE) of the coding regions of the CFTR gene was carried out on 500 classic CF patients of Greek origin and on 134 male infertility subjects (monosymptomatic form of CFTR). A prevention program was applied to 900 individuals. Prenatal diagnosis (PND) was carried out in 167 cases, including 110 with intrauterine bowel echogenicity.

RESULTS Among the 500 CF patients, 83 different mutations were characterized, accounting for 92% of CF genes. Mutation testing on 134 male infertility subjects showed that 56.2% of bilateral absent vas deferens (CBAVD) males were carriers and 27.1% were compound heterozygotes. Of the obstructive azoospermia (OA) males, 27.5% had at least 1 CF allele while only 13% of the severe oligospermia males were carriers. Mutation analysis on 900 individuals identified a total of 188 heterozygotes the majority amongst siblings and relatives of index cases. PND revealed 41 affected, 80 heterozygous, and 46 normal fetuses. Of the echogenic bowel fetuses, 15 had one detectable mutation and 4 were homozygotes.

CONCLUSIONS Accurate knowledge of CF mutations provides information for CF prevention programs applicable through heterozygote screening and prenatal diagnosis.

Key words: CBAVD, Cystic fibrosis, Echogenic bowel, ICP, Mutation screening, Obstructive azoospermia, Oligospermia, Prenatal diagnosis.

© Archives of Hellenic Medicine