Informativity of Intragenic Microsatellites for Carrier Detection
and Prenatal Diagnosis of Cystic Fibrosis in the Italian Population
C. Magnani, L. Cremonesi, E. Belloni, M. Ferrari, M. Seia,
M.P. Russo, M. Devoto, P. Ronchetto, G. Romeo
Clinical Genetics , 45(3),135--139 (1994 Mar)
Abstract
Molecular diagnosis of cystic fibrosis (CF) in the Italian
population, based on the detection of the deltaF508 mutation (51.2%
of CF chromosomes), provides full informativity for prenatal
diagnosis (PDN) in about 28% of families at risk. Identification of
the predominant non-deltaF508 mutations allows the characterization
of about 70% of CF chromosomes, making approximately 48% of couples
fully informative. In families where at least one chromosome remains
uncharacterized, allele segregation is still determined using RFLPs
closely linked to the CF gene. The recent identification of three
polymorphic clusters of dinucleotide repeats (IVS8/GT, IVS17b/TA and
IVS17b/CA) led us to evaluate whether their analysis might improve
feasibility studies for prenatal diagnosis or heterozygote
identification. One hundred nuclear families with a CF child,
reflecting the general Italian deltaF508 mutation distribution, were
genotyped for the three microsatellites. In this study
microsatellite analysis using IVS8/GT and IVS17b/TA allowed the
identification of both parental CF chromosomes in 94% of couples;
inclusion in the study of the less polymorphic repeat locus,
IVS17b/CA, slightly improved this percentage (97%). Hence, a
strategy involving primarily the detection of the deltaF508 mutation
and secondarily microsatellite analysis makes possible PDN of CF in
virtually all Italian CF families.
