ABCMdb

PMID: 24106596

Mehdizadeh Hakkak A, Keramatipour M, Talebi S, Brook A, Tavakol Afshari J, Raazi A, Kianifar HR
Analysis of CFTR Gene Mutations in Children with Cystic Fibrosis, First Report from North-East of Iran.
Iran J Basic Med Sci. 2013 Aug;16(8):917-21., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC7 p.Arg347Pro PCR-RFLP was done for detection of R344W and R347P, and PCR-Sequencing was performed for exon 11 in patients with unidentified mutation throughout previous steps. Login to comment 7 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser466* ABCC7 p.Leu467Phe Results: Among 112 alleles, 24 mutated alleles (21.42%) were detected: ƊF508 (10.71%), 1677delTA (3.57%), S466X (3.57%), N1303K (0.89%), G542X (0.89%), R344W (0.89%), L467F (0.89%). Login to comment 20 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Although, the prevalence and types of mutations vary in different populations based on their geographic and ethnic origins (9, 10), a few mutations (p.F508del, p.G542X, p.N1303K, p.G551D, p.W1282X) have higher frequencies than others. Login to comment 41 ABCC7 p.Asn1303Lys To detect the target mutations, three steps were taken: The first step was performing amplification refractory mutation system assay (ARMS-PCR) detecting common CFTR mutations based on previous reports in Iran and neighboring countries (p.Phe508del, p.Gly542X, p.Asn1303Lys) in all DNA samples following description of Ferrie et al (17). Login to comment 42 ABCC7 p.Arg347Pro In the second step, restriction fragment length polymorphism technique (PCR-RFLP) was used to investigate p.Arg1303Lys and p.Arg347Pro mutations in exon eight. Login to comment 49 ABCC7 p.Asn1303Lys Identification of mutations Performing ARMS-PCR for four common CFTR mutations resulted in identification of 14 mutated chromosomes: p.Phe508del in 12 chromosomes (five homozygote and two heterozygote patients), p.Gly542X in one chromosome and p.Asn1303Lys in one chromosome as well. Login to comment 53 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser466* ABCC7 p.Ser466* ABCC7 p.Ser466* ABCC7 p.Ser466* ABCC7 p.Leu467Phe Demographic, clinical, and family characterizations of patients with specific CFTR mutation No of patients Sex Sweat chloride (meq/lit) Pancreatic insufficiency Age of clinical presentation onset (month) First clinical symptom/sign Consanguinity of parents Mutation status 1 M 110 + 6 Steatorrhea/Hepatomegaly First cousin ƊF508/ ƊF508 2 M 115 + 5 Steatorrhea/Cough/ Hepatomegaly First cousin ƊF508/ ƊF508 3 F 130 + 2 Steatorrhea/Cough Wheezing/Skin rash First cousin ƊF508/ ƊF508 4 F 180 + 1 Steatorrhea/Cough/Vomiting/E dema/Hepatomegaly First cousin ƊF508/ ƊF508 5 M 93 + 3.5 FTT/Steatorrhea First cousin once removed ƊF508/ ƊF508 6 M 100 + At birth Wheezing/Meconium ileus - ƊF508/U* 7 M 115 + 2 Steatorrhea/Cough/Fever First cousin once removed ƊF508/U 8 M 90 + 6 Cough/Wheezing - N1303K/U 9 F 70 + At birth Meconium ileus/Crackle First cousin G542X/U 10 F 80 - 5 Cough/Wheezing/Fever - R334W/U 11 M 109 + 1 Fever/Wheezing/Cough Second cousin S466X/ S466X 12 M 120 + 10 Cough/Wheezing/Steatorrhea - S466X/U 13 M 100 + At birth Wheezing/Meconium ileus First cousin S466X/U 14 M 100 + 5.5 Rectal prolapse/Cough/ Wheezing/Steatorrhea First cousin 1677delTA/ 1677delTA 15 M 85 + 3 FTT/Sreatorrhea/Wheezing/ Cough First cousin 1677delTA/ 1677delTA 16 F 93 + 4 Steatorrhea - 1531C/T (L467F)/U * Unknown mutation PCR-RFLP was operated for identification of p.Arg334Trp and p.Arg347Pro mutations and revealed only one heterozygote status for p.Arg334Trp mutation. Login to comment 56 ABCC7 p.Leu467Phe p.Tyr515X was detected in four chromosomes (two homozygotes), p.Ser466X also in four chromosomes (one homozygote and two heterozygotes) and p.Leu467Phe in one chromosome (Table 3). Login to comment 59 ABCC7 p.Asn1303Lys We initially detected three of common CFTR mutations among Iranian CF patients which were identified in previous studies (13) (p.Phe508del, p.Asn1303Lys, and p.Gly542X) using ARMS-PCR. Login to comment 60 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro Exon eight was probed for p.Arg334Trp and p.Arg347Pro mutations by PCR-RFLP which revealed only one p.Arg334Trp mutation. Login to comment 61 ABCC7 p.Leu467Phe At final step we focused on PCR-Sequencing for exon 11 in patients who remained incompletely identified for CFTR mutation in any of CFTR alleles, resulting in identification of nine other mutated chromosomes (p.Ser466X, p.Tyr515X, and p.Leu467Phe) in addition to p.Phe508del mutation. Login to comment 65 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser466* ABCC7 p.Leu467Phe ABCC7 p.Leu467Phe Total chromosomes: 100%, known mutations: 21.42%, unknown mutations: 78.58% cDNA name Protein name Legacy name Number of chromosomes detected Exon/Intron Description Detection method c.1000C>T p.Arg334Trp R334W 1 (0.89* -4.16 &#f0ff; ) Exon 8 C to T at 1132 PCR-RFLP c.1397C>G p.Ser466X S466X 4 (3.57 - 16.66) Exon 11 C to G at 1529 Sequencing c.1399C>T p.Leu467Phe 1531C/T (L467F) 1 (0.89 - 4.16) Exon 11 C or T at 1531 Sequencing c.1521-1523delCTT p.Phe508del ƊF508 12 (10/71 - 50) Exon 11 deletion of 3 bp between 1652 and 1655 ARMS and Sequencing c.1545-1546delTA p.Tyr515X 1677delTA 4 (3.57 - 16.66) Exon 11 deletion of TA from 1677 Sequencing c.1624G>T p.Gly542X G542X 1 (0.89 - 4.16) Exon 12 G to T at 1756 ARMS c.3909C>G p.Asn1303Lys N1303K 1 (0.89 - 4.16) Exon 24 C to G at 4041 ARMS * % of all analyzed chromosomes &#f0ff; % of all mutated chromosomes Alibakhshi et al (2008) (13) explored 69 Iranian CF patients sampled from different geographic areas and ethnic groups around Iran. Login to comment 73 ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Leu467Phe ABCC7 p.Leu467Phe (26, 27) The p.Asn1303Lys, p.Gly542X, p.Arg334Trp, p.Leu467Phe (L467F) mutations, each had a frequency of approximately 4.1% of all detected mutations and 0.9% of all analyzed chromosomes. Login to comment 74 ABCC7 p.Asn1303Lys p.Asn1303Lys has a high frequency among Mediterranean countries and was reported as the second frequent mutation in Iran, (28) Lebanon (29) and Algeria (30) and third common mutation in Libya (31) and Tunisia. Login to comment 75 ABCC7 p.Asn1303Lys (32) Current findings introduced p.Asn1303Lys as the fourth common detected mutation in North Eastern Iran. Login to comment 77 ABCC7 p.Arg334Trp (37) p.Arg334Trp is more frequent in South American countries and is considered to be associated with greater risk for pancreatitis and renal proteinuria, (38, 39) while the patient carrying this mutation in our study suffered from pancreatic insufficiency and mild proteinuria. Login to comment 78 ABCC7 p.Leu467Phe p.Leu467Phe is a rare mutation and was first identified in France. Login to comment