First-trimester prenatal screening for the common 35delG GJB2 mutation causing prelingual deafness.
OBJECTIVE
This study evaluates the prevalence of 35delG GJB2 mutation, the most common genetic mutation causing prelingual deafness, and its screening feasibility and acceptability in pregnant women undergoing first-trimester CVS for chromosomal abnormality investigation.


METHODS
Samples were taken from 5786 pregnant women who requested CVS for chromosomal analysis. The samples were split into two aliquots for chromosome and DNA analysis, respectively. The results of foetal karyotyping were provided 7 days after sampling, at which time the fully informed couple decided whether or not to undergo DNA testing.


RESULTS
Of the 5449 eligible candidates, 2997 (55.0%) chose to undergo 35delG testing. Among them, 67 proved to be carriers of the mutation, resulting in a prevalence rate of 1:44.7 (2.23%). There were no homozygous foetuses, but two double heterozygous foetuses were found, and in one case the couple chose to terminate the pregnancy.


CONCLUSIONS
The results confirm the high frequency of 35delG mutation in the Italian population. The study shows that prenatal screening for GJB2 mutations in pregnant women with no retrospective risk for deafness appears to be feasible and highly acceptable. Consequently, given evidence that early evaluation and treatment significantly improve speech and language skills, as well as social and emotional well-being in affected children, 35delG mutation analysis in pregnant women booking CVS primarily for chromosomal investigation could be considered a useful addition to more comprehensive population screening strategies.
Laboratorio di Genetica Medica, Istituti Clinici di Perfezionamento, Milan, Italy.
Domenico A
DA
Coviello
Bruno
B
Brambati
Lucia
L
Tului
Antonio
A
Percesepe
Francesca
F
Sironi
Achal
A
Sahai
Roberto
R
Bertorelli
Antonino
A
Forabosco
D015193:Chorionic Villi Sampling; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005865:Gestational Age; D006579:Heterozygote; D006801:Humans; D007558:Italy; D007621:Karyotyping; D009154:Mutation; D011247:Pregnancy; D011261:Pregnancy Trimester, First
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26