ABCMdb

PMID: 18782298

Sharma N, Singh M, Kaur G, Thapa BR, Prasad R
Identification and characterization of CFTR gene mutations in Indian CF patients.
Ann Hum Genet. 2009 Jan;73(1):26-33. Epub 2008 Sep 8., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Ser158Asn ABCC7 p.Ile530Leu ABCC7 p.Glu1329Gln ABCC7 p.Gln493Leu ABCC7 p.Leu69His We report identification of 14 previously known and eight novel mutations, namely 3986-3987delC, 876-6del4, 1792InsA, L69H, S158N, Q493L, I530L and E1329Q. Login to comment 41 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Seven other mutations were searched for by either single ARMS PCR (R117H, N1303K, and R553X) or by multiplex ARMS PCR (621 + 1G-T, G542X, G551D, W1282X). Login to comment 42 ABCC7 p.Ala455Glu ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg1162* CFTR mutations investigated by restriction analysis of PCR products were R334W (MspI), R347P (NcoI), A455E (AciI), 2789+5G-A (SSPI), R1162X (DdeI), and 3849+10kb C-T (HphI) (Gasparini et al., 1991; Dean et al., 1990; Kerem et al., 1990; Highsmith et al., 1990). Login to comment 64 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Asn1303Lys R117H, R553X, N1303K & G551D were identified by ARMS on a total of five chromosomes. Login to comment 67 ABCC7 p.Val520Phe ABCC7 p.Ser549Asn ABCC7 p.Leu218* ABCC7 p.Ser158Asn ABCC7 p.Ile530Leu ABCC7 p.Glu1329Gln ABCC7 p.Gln493Leu ABCC7 p.Leu69His ABCC7 p.Tyr1381His ABCC7 p.Tyr517Cys They included nine missense mutations (L69H, S158N, Q493L, Y517C, V520F, I530L, S549N, E1329Q, and Y1381H), one insertion mutation (1792insA), three splice site mutations (876-6del4, 1525-1G-A, 3120+1G-A), two deletion mutations (1161delC, 3986delC), and 1 nonsense mutation (L218X). Login to comment 68 ABCC7 p.Ser549Asn S549N and 1525-1G-A were the second most common mutations observed in our population (5% each). Login to comment 73 ABCC7 p.Ser158Asn ABCC7 p.Ile530Leu ABCC7 p.Glu1329Gln ABCC7 p.Gln493Leu ABCC7 p.Leu69His Novel Mutations and Phenotypic Features Output prediction scores were assessed for five novel mutations; they were >0.5 for L69H & Q493L and <0.5 for S158N, I530L & E1329Q (Table 3). Login to comment 74 ABCC7 p.Leu69His ABCC7 p.Leu69His L69H L69H was identified on one allele in a 3 month old baby with a history of vomiting and coughs for the last month. Login to comment 79 ABCC7 p.Ser158Asn ABCC7 p.Ser158Asn S158N The chief complaint of the 13 yr old patient, compound heterozygous for S158N, was recurrent coughs for the last five years. Login to comment 85 ABCC7 p.Gln493Leu ABCC7 p.Gln493Leu Q493L The 3 yr old patient heterozygous for Q493L had complaints of chronic coughs and vomiting. Login to comment 89 ABCC7 p.Ile530Leu ABCC7 p.Ile530Leu I530L The 4 month old female child born to a consanguineous marriage had a homozygous I530L genotype and presented with recurrent respiratory infections and loose stools since 2 months of age. Login to comment 93 ABCC7 p.Glu1329Gln ABCC7 p.Glu1329Gln E1329Q The 11 yr old male child heterozygous for E1329Q had a history of frequent episodes of coughing and difficulty in breathing since 2 years of age, on and off abdominal distension, and voluminous oily stools. Login to comment 96 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Val520Phe ABCC7 p.Ser549Asn ABCC7 p.Ser549Asn ABCC7 p.Leu218* ABCC7 p.Ser158Asn ABCC7 p.Ile530Leu ABCC7 p.Ile530Leu ABCC7 p.Glu1329Gln ABCC7 p.Gln493Leu ABCC7 p.Leu69His ABCC7 p.Tyr1381His ABCC7 p.Tyr1381His ABCC7 p.Tyr517Cys Table 2 Genotypes of CF subjects (n=50) Genotype Number of subjects Delta F508/Delta F508 5 Delta F508/3849+10kb C-T 1 Delta F508/S549N 2 Delta F508/S158N 1 Delta F508/Y1381H 1 Delta F508/1525-1 G-A 2 V520F/R117H 1 I530L/I530L 1 876-6del4/876-6del4 1 1792ins A/1792insA 1 3986-3987delC/3986-3987delC 1 Delta F508/U 10 1161 delC/U 2 L69H/U 1 R117H/U 1 Q493L/U 1 Y517C/U 1 S549N/U 3 G551D/U 1 E1329Q/U 1 N1303K/U 1 Y1381H/U 1 L218X/U 1 R553X/U 1 1525-1G-A/U 3 3120+1G-A/U 2 3849+10kb C-T/U 2 U/U 1 U-unidentified Table 3 Outcome prediction scores of novel substitution mutations identified in Indian CF patients Wild type Mutant Position Output Reliablity Prediction L H 69 0.5210 0 Pathological S N 158 0.3304 3 Neutral Q L 493 0.7784 5 Pathological I L 530 0.0591 8 Neutral E Q 1329 0.1018 7 Neutral Molecular Modelling and Bioinformatics (MMB) program (http://mmb.pcb.ub.es/PMut/) was used for pathological predictions of novel sequence variants. Login to comment 113 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Val520Phe ABCC7 p.Ser549Asn ABCC7 p.Leu218* ABCC7 p.Ser158Asn ABCC7 p.Ile530Leu ABCC7 p.Glu1329Gln ABCC7 p.Gln493Leu ABCC7 p.Leu69His ABCC7 p.Tyr1381His ABCC7 p.Tyr517Cys We first identified five of the mutations by ARMS (Delta F508, R117H, R553X, N1303K & G551D) and one by restriction digestion (3849+10kbC-T) and later identified by SSCP eight known (Y517C, V520F, S549N, Y1381H, 1525-1G-A, 3120+1G-A, 1161delC and L218X) and eight previously unreported mutations (L69H, S158N, Q493L, I530L, E1329Q, 876-6del4, 1792insA and 3986-3987delC). Login to comment 119 ABCC7 p.Ser549Asn S549N and 1525-1G-A were the second most common mutations, followed by 3849+10kbC-T. Login to comment 120 ABCC7 p.Ser549Asn This corroborates the study of Shastri et al., (2008) which has recommended testing Indian CF patients for delta F508 followed by 1161delC, 3849+10kbC-T and S549N. Login to comment 133 ABCC7 p.Ser158Asn ABCC7 p.Ile530Leu ABCC7 p.Glu1329Gln ABCC7 p.Gln493Leu ABCC7 p.Leu69His Output prediction scores deduced using molecular modeling and a bioinformatics program (http://mmb.pcb.ub.es/PMut/) revealed that among the novel mutations, L69H and Q493L are pathologic but S158N, I530L and E1329Q are neutral. Login to comment