ABCMdb

PMID: 19833837

Oca F, Dreux S, Gerard B, Simon-Bouy B, de Becdelievre A, Ferec C, Girodon E, Muller F
Amniotic fluid digestive enzyme analysis is useful for identifying CFTR gene mutations of unclear significance.
Clin Chem. 2009 Dec;55(12):2214-7. Epub 2009 Oct 15., [PubMed]

Sentences

No. Mutations Sentence Comment

10 ABCC7 p.Ser1235Arg ABCC7 p.Gly622Asp ABCC7 p.Gly1127Glu ABCC7 p.Leu73Phe ABCC7 p.Asn1224Lys Of the 5 questionable cases (F508del/N1224K, F508del/L73F, 3849ϩ10kbCϾ T/G1127E, F508del/S1235R, F508del/G622D), all were CF symptom free at 2-4 years of follow-up. Login to comment 61 ABCC7 p.Ser1235Arg The fifth case (F508del/S1235R) also presented with a prenatally diagnosed DiGeorge syndrome (cardiac malformation) with an imperforate anus detected at birth (29 weeks). Login to comment 63 ABCC7 p.Ser1235Arg An "obstructive" AF-DE pattern was observed in 2 cases (related to the imperforate anus in the F508del/S1235R case). Login to comment 78 ABCC7 p.Gly1127Glu ABCC7 p.Leu73Phe ABCC7 p.Asn1224Lys In 3 cases (N1224K, L73F, and G1127E), the AF-DE pattern was typical. Login to comment 80 ABCC7 p.Gly1127Glu ABCC7 p.Leu73Phe ABCC7 p.Asn1224Lys F508del was in trans of N1224K and L73F, and the variable CF-causing 3849ϩ10KbCϾT was in trans of G1127E (16). Login to comment 81 ABCC7 p.Ser1235Arg An "obstructive" AF-DE pattern observed in the F508del/S1235R fetus was in fact explained by DiGeorge syndrome (imperforate anus) (14). Login to comment 83 ABCC7 p.Ser1235Arg S1235R was recently considered a CFTR-RD mutation or a neutral variant (10). Login to comment 84 ABCC7 p.Gly622Asp In the last case (F508del/G622D), we have no clear explanation for the abnormal AF-DE pattern. Login to comment 86 ABCC7 p.Gly622Asp The G622D variant, identified in infertile patients, was found at an allelic frequency of 0.18% in a population of African Americans (17). Login to comment 89 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Ser1235Arg ABCC7 p.Gly622Asp ABCC7 p.Gly1127Glu ABCC7 p.Leu73Phe ABCC7 p.Asn1224Lys ABCC7 p.Gln1042* CFTR mutation Cases, n Outcome/follow-up CF/CF mutation (n ϭ 38) F508del/F508del 21 TOPa (n ϭ 20); birth, severe CF (n ϭ 1) F508del/unidentified severe mutationb 3 TOP (n ϭ 3) F508del/G551D 2 TOP (n ϭ 2) F508del/4005ϩ1GϾA 1 TOP F508del/2711delT 1 Birth, severe CF F508del/297-3CϾT 1 TOP F508del/3120ϩ1GϾA 1 TOP F508del/405ϩ1GϾA 1 TOP F508del/711ϩ1GϾT 1 TOP F508del/Q1042X 1 TOP F508del/dele22-23 1 TOP F508del/2789ϩ5GϾA 1 Birth, severe CF dele19/dele19c 1 Birth, severe CF W1282X/dele2-6b 1 TOP 1078delT/394delTT 1 TOP CF/unknown variant (n ϭ 4) F508del/G622D 1 Birth, no clinical sign of CF F508del/N1224K 1 Birth, no clinical sign of CF F508del/L73F 1 Birth, no clinical sign of CF 3849ϩ10kbCϾT/G1127E 1 Birth, no clinical sign of CF CF/CFTR-related disorder (n ϭ 1) F508del/S1235R 1 Birth, no clinical sign of CF (del22q11 ϩ imperforate anus)d a TOP, termination of pregnancy. Login to comment 94 ABCC7 p.Gly622Asp One hypothesis is that the G622D phenotype is clinically expressed in intestinal microvilli only during fetal life and is silent thereafter. Login to comment