ABCMdb

PMID: 12070257

Scotet V, De Braekeleer M, Audrezet MP, Quere I, Mercier B, Dugueperoux I, Andrieux J, Blayau M, Ferec C
Prenatal detection of cystic fibrosis by ultrasonography: a retrospective study of more than 346 000 pregnancies.
J Med Genet. 2002 Jun;39(6):443-8., [PubMed]

Sentences

No. Mutations Sentence Comment

184 ABCC7 p.Gln220* The sweat test performed three months after birth in this last child was positive, and this led to an exhaustive screening of the gene, which identified the second mutation in exon 6a (Q220X). Login to comment 190 ABCC7 p.Trp1282* ABCC7 p.Gln220* Nine of them were homozygotes and five were compound heterozygotes, carrying on the other chromosome a severe mutation which is usually rare in our population: there were two nonsense mutations (Q220X, W1282X), two splice mutations (4005+1 G→A, 1717-1 G→A), and one frameshift mutation (3129del4). Login to comment 196 ABCC7 p.Arg347His ABCC7 p.Gly542* The heterozygous fetuses carried a severe molecular abnormality (∆F508 (n=9) or G542X (n=1)), except one who carried a mild mutation (R347H). Login to comment 202 ABCC7 p.Trp1282* ABCC7 p.Arg347His ABCC7 p.Gly542* ABCC7 p.Gln220* Therefore, the second mutation Table 1 Incidence of cystic fibrosis and CF heterozygosity among fetuses with echogenic bowel in Brittany, France (1991-2000) Fetuses with echogenic bowel 142 Affected fetuses Number 14 Incidence 1/10 Genotypes ∆F508/∆F508 9 ∆F508/4005+1G→A 1 ∆F508/3129del4 1 ∆F508/Q220X 1 ∆F508/W1282X 1 ∆F508/1717-1G→A 1 CF incidence in the general population during the present study 1/2987 Risk of CF: echogenic bowel fetuses/general population 294 Heterozygous fetuses Number 11 Incidence 1/13 Mutations ∆F508 9 G542X 1 R347H 1 CF heterozygosity in the general population during the present study 1/28 Risk of CF heterozygosity: echogenic bowel fetuses/general population 2.2 Letter www.jmedgenet.com will be identified in 88.5% of the 22.6% of fetuses for which the first analysis identified only one mutation (that is, in 20.0% of all CF fetuses). Login to comment 241 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Gly542* ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Asp443Tyr However, they based their comparison on an expected carrier rate in the general population which appears to be overestimated.1 The CFTR mutations identified in fetuses with echogenic bowel that have been reported so far are associated with pancreatic insufficiency (for example, ∆F508, G542X, G551D, Table 2 Ability of the ultrasound examination to detect cystic fibrosis Cystic fibrosis TotalYes No Utrasound examination Abnormal 14 128 142 Normal 112 346 300 346 412 Total 126 346 428 346 554 2183AA→G, ∆F311).9 13 27 43 To our knowledge, only one mutation associated with a mild phenotype (R117H)13 and one mild complex CFTR allele (D443Y-G576A-R668C)44 have been identified in two of the CF affected fetuses. Login to comment 244 ABCC7 p.Arg347His This was also observed in heterozygotes, excepted for one case (mutation R347H). Login to comment 246 ABCC7 p.Arg117His ABCC7 p.Arg347Leu ABCC7 p.Gly91Arg ABCC7 p.Arg560Lys Therefore, the spectrum of mutations identified in this fetal population is not representative of that identified in our CF population, in which we found a significant number of mild mutations or mutations for which the clinical consequences are not yet established (for example, G91R, R117H, R347L, R560K).34 35 These findings provide the foundation for further investigations towards understanding the pathogenesis of early bowel disease, but also why it results in manifestations in the bowel rather than in the lungs during the fetal period. Login to comment