ABCMdb

PMID: 22627569

De Bie I, Agatep R, Scott P, Ruchon A
Report on the p.Ser489X (p.Ser489*) CFTR mutation, a variant with severe associated phenotype and high prevalence in a Quebec French-Canadian cystic fibrosis patient population.
Genet Med. 2012 Oct;14(10):883-6. doi: 10.1038/gim.2012.57. Epub 2012 May 24., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC7 p.Ala455Glu ABCC7 p.Ala455Glu In this population, three Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations account for ~94% of disease alleles, namely p.Phe508del (p.F508del; [delta] F508, c.1521_1523delCTT), 621+1G>T (c.489+1G>T), and p.Ala455Glu (p.A455E; c.1364C>A).3,4 Molecular CFTR testing is usually performed to confirm a clinical diagnosis of CF, to determine carrier status in individuals at risk, or to corroborate results of newborn screening. Login to comment 30 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu All but one of these CF patients ascertained in our French-Canadian cohort were compound heterozygotes for the p.Ser489X variant and another severe disease-causing CFTR allele, namely p.Phe508del, 621+1G>T (c.489+1G>T), 711+1G>T (c.579+1G>T), p.Ile1023_Val1024del (3199del6; c.3067_3072delATAGTG), or p.Gly85Glu (p.G85E; c.254G>A) (Table 1). Login to comment 31 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu All but one of these CF patients ascertained in our French-Canadian cohort were compound heterozygotes for the p.Ser489X variant and another severe disease-causing CFTR allele, namely p.Phe508del, 621+1G>T (c.489+1G>T), 711+1G>T (c.579+1G>T), p.Ile1023_Val1024del (3199del6; c.3067_3072delATAGTG), or p.Gly85Glu (p.G85E; c.254G>A) (Table 1). Login to comment 41 ABCC7 p.Gly85Glu CFTR genotype Age at diagnosis Reported symptoms Note 1 p.[Ser489X];[Ser489X] Newborn Volvulus, meconium ileus, positive trypsinogen 2 p.[Phe508del];[Ser489X] 3 Months Meconium ileus and positive sweat test 3 (Sib of 2) p.[Phe508del];[Ser489X] 1 Week Meconium ileus 4 p.[Phe508del];[Ser489X] 2 Weeks Meconium ileus 5 p.[Phe508del];[Ser489X] 5 Months Positive sweat test, intestinal obstruction, and steatorrhea 6 p.[Phe508del];[Ser489X] 15 Months Positive sweat test, no additional symptoms reported 7 p.[Phe508del];[Ser489X] Unknown Unknown Tested at 7 years of age 8 p.[Phe508del];[Ser489X] Unknown Unknown Tested at 9 years of age 9 p.[Phe508del];[Ser489X] Unknown Unknown Diagnosis made in infancy; molecular testing performed as an adult (26 years old) 10 [621+1G>T];p.[Ser489X] 2 Months Growth restriction, failure to thrive 11 [711+1G>T];p.[Ser489X] 3 Months Positive sweat test, no additional symptoms reported 12 p.[Ile1023_Val1024del]; [Ser489X] Unknown Positive sweat test, no additional symptoms reported Tested at 13 years of age 13 p.[Gly85Glu];[Ser489X] Unknown Unknown Diagnosis made in infancy, molecular testing performed as an adult (18 years old) Genetics in medicine | Volume 14 | Number 10 | October 2012 p.Ser489X, a high-prevalence CFTR variant in a cystic fibrosis patient population | DE BIE et al brief report been mostly characterized in a CF mouse model,7,8 and has only scarcely been reported in the human CF literature.4,9-11 This variant results in premature chain termination and is predicted to behave as a functional class I allele, causing reduced CFTR protein synthesis. Login to comment 42 ABCC7 p.Gly85Glu CFTR genotype Age at diagnosis Reported symptoms Note 1 p.[Ser489X];[Ser489X] Newborn Volvulus, meconium ileus, positive trypsinogen 2 p.[Phe508del];[Ser489X] 3 Months Meconium ileus and positive sweat test 3 (Sib of 2) p.[Phe508del];[Ser489X] 1 Week Meconium ileus 4 p.[Phe508del];[Ser489X] 2 Weeks Meconium ileus 5 p.[Phe508del];[Ser489X] 5 Months Positive sweat test, intestinal obstruction, and steatorrhea 6 p.[Phe508del];[Ser489X] 15 Months Positive sweat test, no additional symptoms reported 7 p.[Phe508del];[Ser489X] Unknown Unknown Tested at 7 years of age 8 p.[Phe508del];[Ser489X] Unknown Unknown Tested at 9 years of age 9 p.[Phe508del];[Ser489X] Unknown Unknown Diagnosis made in infancy; molecular testing performed as an adult (26 years old) 10 [621+1G>T];p.[Ser489X] 2 Months Growth restriction, failure to thrive 11 [711+1G>T];p.[Ser489X] 3 Months Positive sweat test, no additional symptoms reported 12 p.[Ile1023_Val1024del]; [Ser489X] Unknown Positive sweat test, no additional symptoms reported Tested at 13 years of age 13 p.[Gly85Glu];[Ser489X] Unknown Unknown Diagnosis made in infancy, molecular testing performed as an adult (18 years old) Genetics in medicine | Volume 14 | Number 10 | October 2012 p.Ser489X, a high-prevalence CFTR variant in a cystic fibrosis patient population | DE BIE et al brief report been mostly characterized in a CF mouse model,7,8 and has only scarcely been reported in the human CF literature.4,9-11 This variant results in premature chain termination and is predicted to behave as a functional class I allele, causing reduced CFTR protein synthesis. Login to comment 55 ABCC7 p.Ala455Glu ABCC7 p.Arg334Trp ABCC7 p.Gly85Glu Frequencies of CFTR disease-causing alleles in the French-Canadian cystic fibrosis patient population CFTR variant All variants p.Phe508del 621+1G>T 711+1G>T p.Ala455Glu p.Ser489X p.Arg334Trp 3199del6 p.Gly542X p.Gly85Glu p.Ile507del FC SLSJ FC SLSJ FC SLSJ FC SLSJ FC SLSJ FC SLSJ FC SLSJ FC SLSJ FC SLSJ FC SLSJ FC SLSJ Number of CF chromosomes 1712 172 1321 116 143 29 61 1 51 13 12 0 9 0 8 2 6 1 5 1 4 1 % Of total CF chromosomes 100.00 100.00 77.16 67.44 8.35 16.86 3.56 0.58 2.98 7.56 0.70 0.00 0.53 0.00 0.47 1.16 0.35 0.58 0.29 0.58 0.23 0.58 CF, cystic fibrosis; FC, French-Canadian; SLSJ, Saguenay-Lac-St-Jean. Login to comment 61 ABCC7 p.Ala455Glu None of the CF probands of our cohort identified as originating from the SLSJ region were found to be carriers of the p.Ser489X variant, whereas Madore et al.4 had reported this variant in one of their SLSJ CF patients, with an estimated allele frequency of 0.59% for this population.The allele frequencies of two of the three most common SLSJ CFTR mutations, namely p.Phe508del and p.Ala455Glu, are similar in our cohort to those reported by Madore et al.4 for this population. Login to comment 62 ABCC7 p.Ala455Glu None of the CF probands of our cohort identified as originating from the SLSJ region were found to be carriers of the p.Ser489X variant, whereas Madore et al.4 had reported this variant in one of their SLSJ CF patients, with an estimated allele frequency of 0.59% for this population.The allele frequencies of two of the three most common SLSJ CFTR mutations, namely p.Phe508del and p.Ala455Glu, are similar in our cohort to those reported by Madore et al.4 for this population. Login to comment