ABCMdb

PMID: 15365999

Alper OM, Wong LJ, Young S, Pearl M, Graham S, Sherwin J, Nussbaum E, Nielson D, Platzker A, Davies Z, Lieberthal A, Chin T, Shay G, Hardy K, Kharrazi M
Identification of novel and rare mutations in California Hispanic and African American cystic fibrosis patients.
Hum Mutat. 2004 Oct;24(4):353., [PubMed]

Sentences

No. Mutations Sentence Comment

14 ABCC7 p.Gly551Asp ABCC7 p.Asn1303Lys In a worldwide study of more than 43,000 CF chromosomes, 1652_1654del (c.1520_1522del, p.Phe508del) accounted for 66% of the mutations, while the next four most common mutations 1756G>T(c.1624G>T, p. Gly542Ter), 4041C>G(c.3909C>G, p.Asn1303Lys), 1784G>A(c.1652G>A, p. Gly551Asp), 3978G>A(c.3846G>A, p.Trp1282Ter) had relative frequencies of 1.2-2.4 %. Login to comment 63 ABCC7 p.Phe1016Ser A total of eight novel mutations: one missense mutation 3179T>C, (c.3047T>C, p.Phe1016Ser), six frame-shift mutations: 124_146del23bp (c.-9_14del23), 360_365insT (c.233dupT, p.Phe77fs), 379_381insT (c.248dupT, p.Phe83fs), 1285_1288dupTA (c.1153_1154dupTA, p.Tyr385fs), 2289_2295del7insGT (c.2157_2163del7insGT, p.Leu719fs), and 3960_3961delA (c.3828delA, p.Ser1276fs), and one splice-site mutation, were discovered (Table 1A). Login to comment 72 ABCC7 p.Phe1016Ser Novel Mutations Nucleotide change-position Traditional nomenclature Approved nomenclature Protein Mutation/ Effect Exon/ Intron Number of chromosomes 124_146del23bp c.- 9_14del23 No translation initiation 5`UTR 1 296+2T>A c.164+2T>A splice mutation/ truncation int 2 2 (sib) 360_365 insT c.233dupT p.Phe77fs frameshift/ truncation 3 1 379_381 insT c.248dupT p.Phe83fs frameshift/ truncation 3 1 1285_1288dupTA c.1153_1154dupTA p.Tyr385fs frameshift/ truncation 8 6 (1 homo) 2289_2295 del 7bp insGT c.2157_2163del7insGT p.Leu719fs frameshift/ truncation 13 1 3179 T>C c.3047T>C p.Phe1016Ser missense mutation 17a 1 3960_3961 del A c.3828delA p.Ser1276fs frameshift/ truncation 20 1 Mutations identified in African Americans are in bold. Table 1B. Login to comment 73 ABCC7 p.Pro205Ser ABCC7 p.His199Tyr ABCC7 p.Ser492Phe ABCC7 p.Gln98Arg ABCC7 p.Gly1061Arg ABCC7 p.Gln1100Pro Mutations Not Included in 87-Mutation Panel Nucleotide change-position Traditional nomenclature Approved nomenclature Protein Mutation/Effect Exon/ Intron Number of chromosomes 136 C>T c.4C>T p.Gln2Ter nonsense mutation 1 1 355 C>T c.223C>T p.Arg75Ter nonsense mutation 3 1 406-1G>A c.274-1G>A splice mutation/ truncation int 3 9 (1 sib) 424 C>T c.292C>T p.Gln98Ter nonsense mutation 4 1 425 A>G c.293A>G p.Gln98Arg missense mutation 4 2 663 del T c.531delT p.Ile177fs frameshift/ truncation 5 2 (sib) 727 C>T c.595C>T p.His199Tyr missense mutation 6a 5 (1 sib) Nucleotide change-position Traditional nomenclature Approved nomenclature Protein Mutation/Effect Exon/ Intron Number of chromosomes 745 C>T c.613C>T p.Pro205Ser missense mutation 6a 4 1248+1G>A c.1116+1G>A splice mutation/ truncation 7 2 (sib) 1461 ins AGAT c.1326_1327ins4 p.Asp443fs frameshift/ truncation 9 1 1529 C>G c.1397C>G p.Ser466Ter nonsense mutation 10 1 1607 C>T c.1475C>T p.Ser492Phe missense mutation 10 3 1924 del 7bp c.1792_1798del7 p.Lys598fs frameshift/ truncation 13 2 (sib) 2055 del 9bp to A c.1923_1931del9 insA p.Ser641fs frameshift/ truncation 13 2 (homo) 2105_2117 del 13bp insAGAAA c.1973_1985del 13insAGAAA p.Arg658fs frameshift/ truncation 13 3 2184 ins A c.2052dupA p.Gln685fs frameshift/ truncation 13 2 (twin) 3272-26A>G c.3140-26A>G splice mutation/ truncation int 17a 4 (3 rel) 3313 G>C c.3181G>C p.Gly1061Arg missense mutation 17b 1 3431 A>C c.3299A>C p.Gln1100Pro missense mutation 17b 1 3743 G>A c.3611G>A p.Trp1204Ter nonsense mutation 19 5 (1 sib, 1 homo) 4382 del A c.4250delA p.E1417fs frameshift/ truncation 24 1 Sib:1 sibling pair; homo:homozygote; 3 rel: 3 relatives. Login to comment 80 ABCC7 p.Phe1016Ser ABCC7 p.Phe1016Ser 3179 T>C (c.3047T>C, p.Phe1016Ser): The missense mutation p. Phe1016Ser is caused by the transition thymine to cytosine at nucleotide position 3179 in exon 17a of the CFTR gene. Login to comment 82 ABCC7 p.Phe1016Ser p.Phe1016Ser was found in a three year-old Hispanic female patient (# 1, Table 2A) who carries another novel mutation, the 1285_1288dupTA on the other chromosome. Login to comment 92 ABCC7 p.Ser492Phe Patient #3, a five year-old Hispanic male, is heterozygous for 1285_1288dupTA with the other mutant allele being p.Ser492Phe. Login to comment 93 ABCC7 p.Ser492Phe Missense mutation, 1607C>T (p.Ser492Phe), is located at the regulatory domain and has been reported to be a mild class IV mutation (The Cystic Fibrosis Genetic Analysis Consortium 1994). Login to comment 135 ABCC7 p.Ser492Phe ABCC7 p.Phe1016Ser Clinical Presentations of Five Cystic Fibrosis Cases with Novel 1288insTA Mutation # 1 # 2 # 3 # 4 # 5 Agea /age at diagnosis 3y / 4m 19m / 4m 5y / 8m 6y / 6m 4y / 2m Mutation 1 p.Phe1016Ser 406-1G>A p.Ser492Phe 3876delA 1285_1288dupTA Mutation 2 1285_1288dupTA 1285_1288dupTA 1285_1288dupTA 1285_1288dupTA 1285_1288dupTA Sweat Cl-(mEq/L) b 92 84 97 87 91 FVC (%)a n/a n/a 100 72 n/a FEV1 (%)a n/a n/a 88 62 n/a Infection / Complication Probable haemophilus species, M. Catarrhalis S. aureus, P.aeruginosa none S. aureus, S. marcencens, haemophilus species, respiratory syncytial virus infection (RSV) P. aeruginosa, A. terreus, ABPA Height (cm) a percentile) 93cm (10%) 76cm (5%) 115cm (75%) 116.8cm (10-25%) 102cm (50%) Weight (kg) a percentile) 13.8kg (10-25%) 9kg (<5%) 23kg (95%) 19.9kg (10-25%) 16kg (50%) IRT c (ug/dL) n/a n/a n/a 198,2 n/a Meconium ileus no no no no no Pancreatic function PI PI PI PI PI Enzyme Creon 5 (2/meal,1/snack) Ultrase MT 10 (2/meal, 1/snack) Ultrase MT 12 (3/meal, 1/snack) Creon 10 (5/meal,4/snack) Ultrase (2/meal, 1/snack); Viokase (1/2 tsp/ nocturnal G-tube feeding) Ethnicity Hispanic Hispanic Hispanic Hispanic Hispanic National Origin Mexico Mexico and Native American Mexico Mother - Mexico Father - SanSalvador Mexico Sex F F M M M Family History no known family history no known family history no known family history no known family history Parents are 1st cousins Clinical presentation prior to diagnosis severe FTT, pneumonia, GERD FTT, recurrent respiratory tract infections frequent cough, respiratory tract infections recurrent pneumonia FTT Novel mutations indicated in bold. a at blood draw, b age at sweat Cl- is the same as age at diagnosis, c IRT (immunoreactive trypsin) measured from archived Guthrie cards, if available. ABPA: allergic bronchopulmonary aspergillosis, F: female, FEV: Forced expiratory volume, FVC: Forced vital capacity, FTT: Failure to thrive, GERD: gastroesophageal reflux disease, G-tube: gastrointestinal tube, M: male; m: months, MI: meconium ileus, n/a: not available, PI: Pancreatic insufficient, PS: pancreatic sufficient, y: years. Login to comment 140 ABCC7 p.Phe1016Ser Except for the p.Phe1016Ser missense mutation, all of the novel mutations are frame shift or splice-site mutations that produce truncated CFTR proteins, expected to be deleterious. Login to comment