ABCMdb

PMID: 25940043

Corvol H, Thompson KE, Tabary O, le Rouzic P, Guillot L
Translating the genetics of cystic fibrosis to personalized medicine.
Transl Res. 2015 Apr 15. pii: S1931-5244(15)00131-0. doi: 10.1016/j.trsl.2015.04.008., [PubMed]

Sentences

No. Mutations Sentence Comment

35 ABCC7 p.Arg117His ABCC7 p.Arg117His A/p.Arg117His (formerly R117H) mutation. Login to comment 48 ABCC7 p.Gly542* T p.Gly542X (G542X) 2.6% c.1521_1523del p.Phe508del (F508del) 70% c.1652G . Login to comment 49 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp A p.Gly551Asp (G551D) 2% c.350G . Login to comment 50 ABCC7 p.Arg117His ABCC7 p.Arg117His A p.Arg117His (R117H) 1.14% c.265715G . Login to comment 53 ABCC7 p.Trp1282* A p.Trp1282X (W1282X) 1.49% c.3909C . Login to comment 54 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys G p.Asn1303Lys (N1303K) 1.75% c.1679G . Login to comment 55 ABCC7 p.Arg560Thr ABCC7 p.Arg560Thr C p.Arg560Thr (R560T) 0.28% c.1040G . Login to comment 56 ABCC7 p.Arg347Pro ABCC7 p.Arg347Pro C p.Arg347Pro (R347P) 0.33% c.3717 1 12191C . Login to comment 60 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp T p.Arg334Trp (R334W) 0.24% c.298811G . Login to comment 63 ABCC7 p.Arg553* T p.Arg553X (R553X) 0.91% c.254G . Login to comment 64 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu A p.Gly85Glu (G85E) 0.44% c.1364C . Login to comment 65 ABCC7 p.Ala455Glu ABCC7 p.Ala455Glu A p.Ala455Glu (A455E) 0.3% c.1585-1G , A - (1717-1G , A) 0.89% c.2052delA p.Lys684AsnfsX38 (2184delA) 0.16% c.3484C . Login to comment 66 ABCC7 p.Arg1162* T p.Arg1162X (R1162X) 0.48% c.3528delC p.Lys1177serfsX15 (3659delC) 0.035% c.57911G . Login to comment 138 ABCC7 p.Trp1282* In fact, patients with the p.Trp1282X (p.W1282X) were better responders than those carrying other class I mutations.53 In the last international phase III clinical trial, 238 patients older than 6 years were enrolled. Login to comment 148 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp This was initially demonstrated in the CFTR p.Gly551Asp (p.G551D) mutation, which is the most frequent class III mutation, occurring in 2% (heterozygous) of patients with CF worldwide.55 The clinical trial leading to commercialization was a phase III study (Strive study) including 84 patients treated, against 83 with placebo, Fig 1. Login to comment 152 ABCC7 p.Gly551Asp older than 12 years, and carrying at least 1 p.G551D CFTR allele.56 Significant clinical benefits have been shown both for respiratory status (10% of increase for the percent-predicted FEV1 with a decrease in the number of exacerbations) and for the general status (gain of weight, quality of life). Login to comment 154 ABCC7 p.Gly551Asp The extended clinical study (Envision, children aged between 6 and 11 years) showed similar improvements.57 Consequently, in 2012, ivacaftor was approved in the US and in Europe by the Food and Drug Administration (FDA) and the European Medical Agency, respectively, and commercialized under the name of Kalydeco (Vertex) for patients older than 6 years, and with at least 1 p.G551D CFTR allele. Login to comment 155 ABCC7 p.Gly551Ser ABCC7 p.Gly551Ser ABCC7 p.Gly1244Glu ABCC7 p.Gly1244Glu ABCC7 p.Gly1349Asp ABCC7 p.Gly1349Asp ABCC7 p.Ser1255Pro ABCC7 p.Ser1251Asn ABCC7 p.Ser1251Asn ABCC7 p.Ser549Arg ABCC7 p.Ser549Arg ABCC7 p.Ser549Asn ABCC7 p.Ser549Asn ABCC7 p.Gly178Arg ABCC7 p.Gly178Arg Furthermore, Kalydeco has been tested in patients carrying other class III mutations, or targeted class IVand V mutations (sharing functional similarities with the class III).58 The new trials led to an extension of the FDA and European Medical Agency approval to 8 additional gating mutations: p.Gly178Arg (p.G178R), p.Ser549Asn (p.S549N), p.Ser549Arg (p.S549R), p.Gly551Ser (p.G551S), p.Gly1244Glu (p.G1244E), p.Ser1251Asn (p.S1251N), p.Ser1255Pro (pS1255P), and p.Gly1349Asp (p.G1349D).59 Recently, ivacaftor has also been shown to benefit patients carrying the c.350G . Login to comment 156 ABCC7 p.Arg117His ABCC7 p.Arg117His A/p.Arg117His (formerly R117H) mutation, that is relatively common in the CF population, and leads to both defective channel regulation (sharing similarities with the class III mutations) and conduction. Login to comment 157 ABCC7 p.Arg117His ABCC7 p.Arg117His Thus, the FDA also approved ivacaftor as a treatment for CF subjects aged .6 years with at least 1 copy of R117H-CFTR.60 Additionally, ivacaftor is currently being tested in patients carrying non-R117H residual function mutations. Login to comment