ABCMdb

PMID: 22210575

Riveline JP, Rousseau E, Reznik Y, Fetita S, Philippe J, Dechaume A, Hartemann A, Polak M, Petit C, Charpentier G, Gautier JF, Froguel P, Vaxillaire M
Clinical and metabolic features of adult-onset diabetes caused by ABCC8 mutations.
Diabetes Care. 2012 Feb;35(2):248-51. Epub 2011 Dec 30., [PubMed]

Sentences

No. Mutations Sentence Comment

38 ABCC8 p.Cys418Arg ABCC8 p.Arg620Cys ABCC8 p.Pro201Ser Three mutations were previously reported (c.2476C.T/p.R826W in transient NDM [TNDM] (3,4,13), c.1252T.C/p.C418R and c.1858C.T/ p.R620C in congenital hyperinsulinism [CHI] (14,15)), and one mutation is novel (c.601C.G/p.P201S). Login to comment 40 ABCC8 p.Pro201Ser The P201S mutation that lies at a highly conserved residue across mammalian species, in the L0-linker loop of the TMD0-L0 gatekeeper module of SUR1 (16),wasnotpresentin330normoglycemic French subjects. Login to comment 42 ABCC8 p.Cys418Arg ABCC8 p.Arg620Cys Genotyping of C418R and R620C mutations in .4,000 normoglycemic individuals from the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) cohort (18) identified five and one carrier, respectively, suggesting that they may represent rare variants (population carrier frequency of 0.06 and 0.012%) likely not related to disease. Login to comment 44 ABCC8 p.Cys435Arg ABCC8 p.Cys418Arg ABCC8 p.Tyr356Cys ABCC8 p.Tyr356Cys ABCC8 p.Tyr356Cys ABCC8 p.Arg620Cys ABCC8 p.Pro201Ser 1-II.1 2-II.1 3-II.1 3-II.2 4-II.1 4-III.1 4-III.2 D-1 D-2 D-3 D-4 Sex Female Male Male Male Male Female Male Female Male Male Female Mutation R1380H C435R L582 V L582 V Y356C Y356C Y356C P201S C418R R620C R826 W c.4139G.A c.1303T.C c.1744C.G c.1744C.G c.1067A.G c.1067A.G c.1067A.G c.601C.G c.1252T.C c.1858C.T c.2476C.T Previous report NDM (11) NDM (2) NDM (2) d Type 2 diabetes (7) d d None rs67254669* rs58241708* TNDM (4,6,13) Features at diagnosis or at ascertainment Status Diabetes Diabetes Diabetes Diabetes Diabetes Impaired glucose toleranceߤ Normal glucose toleranceߤ Type 2 diabetes Type 2 diabetes Type 2 diabetes Type 2 diabetes Age (years)/BMI (kg/m 2 ) 17/24 15/20 36/21 32/37 39/26 35/20 33/22 53/22 53/31 46/25 49/28 Symptoms Polyuria Polyuria None Obesity None None None Tiredness Hyperglycemia Polyuria None Features at last examination Age (years) 63 39 38 37 74 35 33 80 74 56 58 SU treatment 15 mg/day glyburidex 15 mg/day glyburidex 5 mg/day glyburide 160 mg/day gliclazide 3 mg/day glimepiride None None Glyburide| Glimepiride| Glypizide Glimepiride HbA 1c (%)ߥ 7.3 6.7 6.2 6.4 6.5 5.5 ND 7.4 6.2 6.8 6.2 C-peptide (pmol/mL) 0.08 0.14 ND ND 3.00 ND ND 1.17 2.08 1.90 3.80 All mutations were identified heterozygously in the patients. Login to comment 49 ABCC8 p.Leu582Val ABCC8 p.Cys435Arg A pathogenic role for three mutations (C435R, L582V, and R1380H) is very likely, because NDM was diagnosed in family relatives (this study) or reported by other studies (2,4,11). Login to comment 50 ABCC8 p.Tyr356Cys The previously published Y356C and R826W mutations (4,6,7,13) were functionally demon- stratedtoalter MgATPsensitivityorATPase activity of SUR1, respectively, leading to KATP channel activation with increased resting whole-cell currents (7,13). Login to comment 51 ABCC8 p.Cys418Arg ABCC8 p.Arg620Cys We cannot exclude that two rare variants (C418R and R620C), as previously reported in CHI (14,15) and found here in two diabetic patients, are nonfunctional (i.e., nondeleterious). Login to comment 57 ABCC8 p.Leu582Val ABCC8 p.Cys435Arg A pathogenic role for three mutations (C435R, L582V, and R1380H) is very likely, because NDM was diagnosed in family relatives (this study) or reported by other studies (2,4,11). Login to comment 58 ABCC8 p.Tyr356Cys The previously published Y356C and R826W mutations (4,6,7,13) were functionally demon- stratedtoalter MgATPsensitivityorATPase activity of SUR1, respectively, leading to KATP channel activation with increased resting whole-cell currents (7,13). Login to comment 59 ABCC8 p.Cys418Arg ABCC8 p.Arg620Cys We cannot exclude that two rare variants (C418R and R620C), as previously reported in CHI (14,15) and found here in two diabetic patients, are nonfunctional (i.e., nondeleterious). Login to comment