ABCMdb

PMID: 21429822

Coiana A, Faa' V, Carta D, Puddu R, Cao A, Rosatelli MC
Preconceptional identification of cystic fibrosis carriers in the Sardinian population: A pilot screening program.
J Cyst Fibros. 2011 May;10(3):207-11. doi: 10.1016/j.jcf.2011.02.006. Epub 2011 Mar 22., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile The most common CF allele was the p.Thr338Ile (T338I) (65%), followed by the p.Phe508del (F508del) (22.5%). Login to comment 7 ABCC7 p.Thr338Ile We also identified one couple at risk and an asymptomatic female homozygote for the p.Thr338Ile allele. Login to comment 80 ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile The most common CF allele was the p.Thr338Ile (T338I) (65%), followed by the p.Phe508del (F508del) (22.5%). Login to comment 81 ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys The p.Asn1303Lys, c.2051_2052delAAinsG, c.489+ 1GNT, c.54-5811_164+2187del8108ins182, and p.Arg347Pro mutations were found once, with a frequency of 2.5% each. Login to comment 82 ABCC7 p.Arg347Pro The p.Arg347Pro mutation, never detected in Sardinian patients until now, was reported to have an overall frequency of 0.8% in the Italian population (WHO, [18]). Login to comment 88 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly1244Glu ABCC7 p.Gly1244Glu ABCC7 p.Arg347Pro ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Ser549Arg ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile ABCC7 p.Leu1065Pro ABCC7 p.Leu1065Pro ABCC7 p.Arg1158* ABCC7 p.Gln552* ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Phe508Cys ABCC7 p.Phe508Cys ABCC7 p.Leu1077Pro ABCC7 p.Leu1077Pro ABCC7 p.Arg1066His ABCC7 p.Arg1066His ABCC7 p.Ile502Thr ABCC7 p.Ile502Thr ABCC7 p.Ser912* ABCC7 p.Ser912* Mutation nomenclaturea Alleles (%) T338I (p.Thr338Ile) 26 (65.0) F508del (p.Phe508del) 9 (22.5) N1303K (p.Asn1303Lys) 1 (2.5) 2183AANG (c.2051_2052delAAinsG) 1 (2.5) 621+1GNT (c.489+1GNT) 1 (2.5) exon 2 del (c.54-5811_164+2187del8108ins182) 1 (2.5) R347P (p.Arg347Pro) 1 (2.5) The 3849+10kbCNT (c.3717+12191CNT), G85E (p.Gly85Glu), 2789+5GNA (c.2657+5GNA), W1282X (p.Trp1282X), G1244E (p.Gly1244Glu), 711+5GNA (c.579+5GNA), 711+1GNT (c.579+1GNA), 4016insT (p.Ser1297PhefsX5), G542X (p.Gly542X), 1717-1GNA (c.1585-1GNA), R553X (p.Arg553X), Q552X (p.Gln552X), G551D (p.Gly551Asp), S549R (ANC) (p.Ser549Arg), I507del (p.Ile507del), F508C (p.Phe508Cys), I502T (p.Ile502Thr), 1706del17 (p.Gln525LeufsX37), 1677delTA (p.Tyr515X), R117H (p.Arg117His), D1152H (p.Asp1152His), L1065P (p.Leu1065Pro), R1066H (p.Arg1066His), L1077P (p.Leu1077Pro), 4382delA (p.Glu1418ArgfsX14), R1162X (p.Arg1162X), R1158X (p.Arg1158X), 1259 insA (p.Gln378AlafsX4), 852del22 (p.Gly241GlufsX13), S912X (p.Ser912X), and 991del5bp (p.Asn287LysfsX19) mutations included in the CF panel were not detected in the population tested. Login to comment 92 ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile An asymptomatic 43 year old female homozygous for the p. Thr338Ile (T338I) allele was also identified (Table 3) whose parents, both T338I heterozygotes, were first cousins. Login to comment 121 ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile Our study showed that the most frequent mutation in Sardinia is the p.Thr338Ile (T338I) (65%), a mild mutation previously described by our group in Sardinian CF patients either in homozygous state (11 patients) or in compound heterozygous state with other severe mutations (18 patients) [16,17]. Login to comment 124 ABCC7 p.Thr338Ile Patients homozygous for the T338I mutation are often asymptomatic otherwise showing a very mild phenotype. Login to comment 125 ABCC7 p.Thr338Ile Clinical manifestation of patient compound heterozygotes for T338I and other severe mutation are slightly more severe ranging from isolated azoospermia, with or without CBAVD, to mild CF phenotype characterized by a mild to moderate pulmonary involvement. Login to comment 127 ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile ABCC7 p.Arg1066His Moreover seven patients belonging from both groups (3 patients T338I/T338I, 2 patients T338I/F508del, 1 patient T338I/ 2183AANG, 1 patient T338I/R1066H), affected by azoospermia with no other CF symptoms, were occasionally identified when they requested CF genetic test for assisted reproduction technologies (ART) (Rosatelli, personal communication). Login to comment 128 ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile There is statistically significant difference between the frequency of the p.Thr338Ile (T338I) allele (65%), highlighted in the present study, and the findings of our previous study on Sardinian CF patients (19.3%) (p=0.0001) [12]. Login to comment 132 ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile c Genotype: p.Thr338Ile (T338I) homozygote. Login to comment 134 ABCC7 p.Thr338Ile ABCC7 p.Thr338Ile As alluded above, this discrepancy is likely due to the mild phenotype of patient p.Thr338Ile (T338I) homozygotes or compound heterozygotes which can escape a diagnosis. Login to comment 136 ABCC7 p.Thr338Ile In the counseling session, patients as well as couples at risk should be exhaustively informed about the asymptomatic or mild phenotype of the T338I allele. Login to comment