ABCMdb

PMID: 26500004

Pepermans X, Mellado S, Chialina S, Wagener M, Gallardo L, Lande H, Bordino W, Baran D, Bours V, Leal T
Identification and frequencies of cystic fibrosis mutations in central Argentina.
Clin Biochem. 2015 Oct 21. pii: S0009-9120(15)00473-7. doi: 10.1016/j.clinbiochem.2015.10.007., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC7 p.Leu49Pro Thirty four different mutations, including two new ones, c.2554dupT and p.Leu49Pro, were detected. Login to comment 72 ABCC7 p.Arg334Trp Two CF-causing mutations (p.Phe508del/ p.Arg334Trp) were detected in a child who was excluded from the series based on not evocative and/or unavailable clinical data. Login to comment 81 ABCC7 p.Leu49Pro Two previously unpublished mutations, c.2554dupT (p.Tyr852Leufs*44) and c.146TNC (p.Leu49Pro), were submitted to the CFTR1 database in 2012 and 2013 respectively [13,14]. Login to comment 84 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala In one patient, the variants c.1727G N C (p.Gly576Ala) and c.2002C N T (p.Arg668Cys) were observed. Login to comment 99 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Pro205Ser ABCC7 p.Pro205Ser ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Arg117Cys ABCC7 p.Arg117Cys ABCC7 p.Gly178Arg ABCC7 p.Gly178Arg ABCC7 p.Arg117Pro ABCC7 p.Arg117Pro ABCC7 p.Tyr362* ABCC7 p.Leu49Pro ABCC7 p.Leu49Pro rs name HGVS p. name HGVS c. name Legacy name n (%) Screening panel CFTR1 database CFTR2 database rs199826652 p.Phe508del c.1521_1523delCTT F508del 94 (56.6) Yes Yes CF-causing rs113993959 p.Gly542* c.1624G N T G542X 7 (4.2) Yes Yes CF-causing No p.Asn1303Lys c.3909C N G N1303K 5 (3) Yes Yes CF-causing rs74767530 p.Arg1162* c.3484C N T R1162X 4 (2.4) Yes Yes CF-causing rs75961395 p.Gly85Glu c.254G N A G85E 3 (1.8) Yes Yes CF-causing rs78756941 NA c.489 + 1G N T 621 + 1G N T 3 (1.8) Yes Yes CF-causing rs76713772 NA c.1585-1G N A 1717-1G N A 3 (1.8) Yes Yes CF-causing No p.Lys684Serfs*38 c.2051_2052delAAinsG 2183AA N G 3 (1.8) Yes Yes CF-causing rs397508173 p.Ser4* c.11C N A S4X 2 (1.2) No Yes No rs121909011 p.Arg334Trp c.1000C N T R334W 2 (1.2) Yes Yes CF-causing rs77010898 p.Trp1282* c.3846G N A W1282X 2 (1.2) Yes Yes CF-causing rs397508141 p.Leu34_Gln39del c.100_117delTTGTCAGACATATACCAA 232del18 1 (0.6) No Yes No No p.Leu49Pro c.146 T N C L49P &#a7; 1 (0.6) No No No rs77834169 p.Arg117Cys c.349C N T R117C 1 (0.6) Yes Yes CF-causing No p.Arg117Pro c.350G N C R117P 1 (0.6) No Yes No rs80282562 p.Gly178Arg c.532G N A G178R 1 (0.6) Yes Yes CF-causing rs121908803 p.Pro205Ser c.613C N T P205S 1 (0.6) No Yes CF-causing rs121908752 p.Leu206Trp c.617 T N G L206W 1 (0.6) Yes Yes CF-causing No p.Arg347Pro c.1040G N C R347P 1 (0.6) Yes Yes CF-causing rs397508155 p.Tyr362* c.1086 T N A Y362X 1 (0.6) No Yes No rs74597325 p.Arg553* c.1657C N T R553X 1 (0.6) Yes Yes CF-causing rs1800098 + rs1800100 p.[Gly576Ala(;)Arg668Cys] c. Login to comment 100 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Ser737Phe ABCC7 p.Ser737Phe ABCC7 p.Ser589Ile ABCC7 p.Ser589Ile ABCC7 p.Leu1414Phe [1727G N C(;)2002C N T] G576A-R668C 1 (0.6) No Yes in trans non CF-causing in trans No p.Ser589Ile c.1766G N T S589I 1 (0.6) No Yes No No NA c.1766 + 1G N A 1898 + 1G N A 1 (0.6) Yes Yes CF-causing rs186089140 p.Ser737Phe c.2210C N T S737F 1 (0.6) No Yes No rs397508376 p.Leu812Phefs*11 c.2434_2435insT 2566insT 1 (0.6) No Yes No No p.Ser821Argfs*4 c.2462_2463delGT 2594delGT 1 (0.6) No Yes CF-causing No p.Tyr852Leufs*44 c.2554dupT c.2554dupT &#a7; 1 (0.6) No No No rs80224560 NA c.2657 + 5G N A 2789 + 5G N A 1 (0.6) No Yes CF-causing rs75096551 NA c.2988 + 1G N A 3120 + 1G N A 1 (0.6) Yes Yes CF-causing rs76151804 NA c.3140-26A N G 3272-26A N G 1 (0.6) No Yes CF-causing rs143570767 NA c.3873 + 1G N A 4005 + 1G N A 1 (0.6) No Yes CF-causing rs397508631 p.Ser1297Phefs*5 c.3884_3885insT 4016insT 1 (0.6) No Yes CF-causing No p.Leu1414Phe c.4242_4242 + 1delGGinsTT 4374_4374 + 1GG N TT 1 (0.6) No Yes No No NA c.1210-12T [5] TG11-5T 1 (0.6) Yes Yes Varying clinical consequence - p.= c.= WT 14 (8.4) NA NA NA HGVS (Human Genoma Variation Society) used for protein nomenclature [15,16]. Login to comment 113 ABCC7 p.Asn1303Lys ABCC7 p.Gly85Glu Genotypes associated with nasal polyps were p.Phe508del/p.Phe508del, p.Phe508del/p.Gly85Glu and p.Gly542*/p.Asn1303Lys. Login to comment 126 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Pro205Ser ABCC7 p.Leu206Trp ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Arg117Cys ABCC7 p.Gly178Arg ABCC7 p.Arg117Pro ABCC7 p.Ser737Phe ABCC7 p.Ser589Ile ABCC7 p.Leu49Pro Genotype N Frequency (%) Total N Total frequency (%) Category I: p.Phe508del/p.Phe508del p.Phe508del/p.Phe508del 30 36.1 30 36.1 Category II: p.Phe508del/Other p.Phe508del/p.Gly542* 5 6 p.Phe508del/p.Asn1303Lys 3 3.6 p.Phe508del/p.Gly85Glu 2 2.4 p.Phe508del/c.1585-1G N A 2 2.4 p.Phe508del/c.2051_2052delAAinsG 2 2.4 p.Phe508del/p.Trp1282* 2 2.4 p.Phe508del/p.Arg117Pro 1 1.2 p.Phe508del/p.Pro205Ser 1 1.2 p.Phe508del/p.Leu206Trp 1 1.2 p.Phe508del/p.Arg553* 1 1.2 p.Phe508del/p.Ser589Ile 1 1.2 p.Phe508del/p.Ser737Phe 1 1.2 p.Phe508del/p.Arg1162* 1 1.2 p.Phe508del/c.1766 + 1G N A 1 1.2 p.Phe508del/p.Leu34_Gln39del 1 1.2 p.Phe508del/p.Leu812Phefs*11 1 1.2 p.Phe508del/c.3140-26A N G 1 1.2 p.Phe508del/c.3873 + 1G N A 1 1.2 p.Phe508del/p.Ser1297Phefs*5 1 1.2 p.Phe508del/c.4242_4242 + 1delGGinsTT 1 1.2 p.Phe508del/c.489 + 1G N T 1 1.2 31 37.5 Category III: Other/other p.Gly542*/p.Asn1303Lys 1 1.2 p.Asn1303Lys/p.Gly85Glu 1 1.2 c.489 + 1G N T/p.Lys684Serfs*38 1 1.2 c.489 + 1G N T/p.Gly542* 1 1.2 p.Arg1162*/p.Ser4* 1 1.2 p.Arg1162*/p.Tyr362* 1 1.2 p.Arg334Trp/c.1585-1G N A 1 1.2 p.Arg334Trp/p.Ser821Argfs*4 1 1.2 p.Arg347Pro/p.Ser4* 1 1.2 c.2657 + 5G N A/p.Tyr852Leufs*44 # 1 1.2 p.Arg1162*/p.Leu49Pro # 1 1.2 11 13.2 Category IV: A single mutation p.Phe508del/WT 3 3.6 c.2988 + 1G N A/WT 1 1.2 p.Arg117Cys/WT 1 1.2 p.Gly178Arg/WT 1 1.2 p.[Gly576Ala(;)Arg668Cys]/TG11-5T 1 1.2 7 8.4 Category V: Wild type 4 4.8 #: new mutation submitted to CFTR1 database [1]; other = other mutation than p.Phe508del. Login to comment 132 ABCC7 p.Leu49Pro The substitution leads to a missense mutation replacing a leucine, an amino acid highly phylogenetically conserved at position 49, by a proline (p.Leu49Pro). Login to comment 142 ABCC7 p.Arg334Trp The child presenting two classical mutations (p.Phe508del/p.Arg334Trp) was initially excluded because no evocative symptoms of CF were present up to nine years of age when DNA was sampled. Login to comment 148 ABCC7 p.Arg334Trp Indeed, patients with p.Phe508del/ p.Arg334Trp have, at least at younger ages (b20 years), a more moderate phenotype with a better preserved lung function than p.Phe508del homozygous patients [2]. Login to comment 156 ABCC7 p.Asn1303Lys The three most common mutations were p.Phe508del, p.Gly542* and p.Asn1303Lys. Login to comment 168 ABCC7 p.Asn1303Lys The frequency we found for the p.Asn1303Lys mutation (3%) is of the same order of magnitude as that reported in studies conducted in Uruguay (2.9%) [20] or in Buenos Aires (2.73%) [18]. Login to comment 172 ABCC7 p.Leu49Pro The two new c.2554dupT and p.Leu49Pro variants we identified are likely disease-causing mutations; they are not reported in human genome databases [22,23]. Login to comment 183 ABCC7 p.Arg1066Cys Considering the development of a panel presenting a high detection rate to be used in both provinces, we suggest to insert three additional mutations (p.Arg1066Cys, c.1680-886A N G and c.3528delC) found at least twice in the Cordoba province [5]. Login to comment 185 ABCC7 p.Ser589Ile Among the 21 mutations, three p.Ser589Ile (0.9%), p.Ser4* (0.6%) and c.3873+1GNA (0.6%) are not included in any first-line test. Login to comment