ABCMdb

PMID: 10922395

Abramowicz MJ, Dessars B, Sevens C, Goossens M, Girodon-Boulandet E
Fetal bowel hyperechogenicity may indicate mild atypical cystic fibrosis: a case associated with a complex CFTR allele.
J Med Genet. 2000 Aug;37(8):E15., [PubMed]

Sentences

No. Mutations Sentence Comment

14 ABCC7 p.Asn1303Lys The N1303K mutation was found in the fetus and the father and no mutation was found on the maternal allele or in the mother. Login to comment 17 ABCC7 p.Asn1303Lys The routine DNA analysis showed the presence of the paternal N1303K mutation in both the younger and the older brother. Login to comment 18 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Asp443Tyr CFTR gene studies were pursued using a DGGE scanning strategy,8 9 and the maternal CFTR allele was found to carry three missense mutations, D443Y (1459G>T, exon 9), G576A (1859G>C, exon 12), and R668C (2134C>T exon 13), which have each previously been reported in males with CBAVD.10-12 On further analysis, the complex mutated maternal allele was found in the younger boy. Login to comment 25 ABCC7 p.Asn1303Lys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Asp443Tyr The two brothers and fetus are compound heterozygotes for the N1303K mutation and the complex CFTR allele D443Y-G576A-R668C. Login to comment 29 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr N1303K N D443Y G576A R668C N D443Y G576A R668C N1303K D443Y G576A R668C N1303K D443Y G576A R668C N1303K Electronic letter of 3 www.jmedgenet.com a regular basis and propose the following approach. Login to comment 39 ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr D443Y, G576A, and R668C have been observed independently or in pairs, in patients with a CF related syndrome for whom the whole CFTR coding sequence has been analysed: D443Y, G576A, R668C, D443Y-G576A, D443Y-R668C in CBAVD patients10-12 and G576A-R668C in a patient with disseminated bronchiectasis, but with no other CF causing mutation found in trans.15 To our knowledge, the D443Y mutation was only observed in CBAVD patients.11 12 The G576A and R668C variations have both initially been described as polymorphisms since they were found on the non-CF chromosome of the mother of a CF child.8 However, they were later considered as putative mild mutations associated with a CBAVD phenotype when combined in trans with F508.16 17 These genotypes may possibly not be disease causing in women. Login to comment 44 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp Indeed, mild CFTR mutations or variants combined in cis may produce a more deleterious eVect than each mutation alone, as was recently shown by functional studies in transfected cells for the D1270N-R74W mutations,18 confirming previous observations.19 20 The identification of an increasing number of complex alleles3 21 may partly account for the diYculties in establishing genotype-phenotype correlations. Login to comment 45 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Trp846* In another fetus with FBH at 21 weeks` gestation, we found the genotype W846X/G576A-R668C. Login to comment 48 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Asp443Tyr It is thus possible that, in our family, the D443Y variation worsens a very mild deleterious eVect of the G576A-R668C allele, or vice versa, accounting for the abnormal sweat test and, perhaps, the respiratory infections in the younger brother. Login to comment