ABCMdb

ABCC8 p.Ala355Thr

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Publications

PMID: 20943779 [PubMed] Ismail D et al: "Familial focal congenital hyperinsulinism."

No. Sentence Comment

9 An Fluorine-18-L-dihydroxyphenylalanine positron emission-computerised tomography scan showed a 7-mm focal lesion in the posterior sectionoftheheadofthepancreas.Bothsiblingswerefoundtobeheterozygousfortwopaternally inherited ABCC8 mutations, A355T and R1494W. Login to comment
68 Genetics ABCC8 sequencing analysis identified two heterozygous mutations, A355T (c.1063GϾA) and R1494W (c.4480CϾT). Login to comment
70 In contrast, the A355T mutation is novel, and although it affects a residue that is wellconservedacrossspecies,itspathogenicityiscurrently uncertain. Login to comment
74 The heterozygous germ line mutations (A355T; R1494W) are therefore likely to be homozygous within the focal lesion. Login to comment
87 The R1494W mutation is a loss of function mutation that has been identified in at least sixunrelatedprobandswithCHItodate(11).Incontrast,the A355T mutation is novel, and although it affects a residue that is well conserved across species, its pathogenicity is currently uncertain. Login to comment

PMID: 21544516 [PubMed] Russo L et al: "Permanent diabetes during the first year of life: multiple gene screening in 54 patients."

No. Sentence Comment

41 The other patient (group 2) Table 1 Clinical and genetic features of patients with diabetes onset within the first year of life studied in the present investigation Patient T1D autoantibodies tested Age at onset (days) Gene variant Other features SU treatment Group 1 nd-VI/1 ICA, GADA, IA-2A 1 KCNJ11/V59A DEND Yes nd-BR/1 None 2 - Diarrhoea nd-RM/4 IAA, GADA, IA-2A 2 KCNJ11/R201S Yes nd-MI/3 IAA, GADA, IA-2A, ZnT8A 2 KCNJ11/R201C Yes nd-PD/2 None 3 ABCC8/L213P DEND Yes nd-FI/1 None 15 ABCC8/V324M; ABCC8/W688R Yes nd-CT/2 None 27 - nd-MI/2 ICA, GADA, IA-2A 38 KCNJ11/K170R Yes nd-LE/2 ICA, IAA, GADA, IA-2A 39 - nd-PR/2 None 40 ABCC8/L213P iDEND Yes nd-NA/1 None 40 KCNJ11/R201C Yes + insulin nd-CT/1 none 60 KCNJ11/V59M iDEND Yes nd-NA/2 ICA, GADA, IA-2A 71 ABCC8/A355T Anaemia Yes + insulin nd-MO/3 ICA, IAA, GADA 73 KCNJ11/H46Y Yes nd-RM/4 IAA, GADA, IA-2A 80 - nd-TO/3 GADA, IA-2A 82 - nd-TS/2 None 120 KCNJ11/V59M iDEND Yes nd-RM/6 None 120 KCNJ11/R195Ha nd-RM/5 IAA, GADA, IA-2A 135 KCNJ11/E322K Yes nd-PI/1 ICA 141 - nd-BG/1 GADA 180 ABCC8/S1054Na nd-CES/3 None 190 - Group 2 mdi-RM/3 None 220 KCNJ11/V59M iDEND Yes mdi/NA-B/1 ICA 251 - mdi-PA/1 ICA, IAA, GADA, IA-2A 270 - mdi-RM-OBG/1 IAA, GADA 289 - Muscle hypotrophy mdi-CES/1 ICA, IAA 300 - mdi-RM-OBG/3 IAA, GADA, IA-2A 330 - mdi-RM-OBG/2 IAA, GADA, IA-2A 330 - mdi-NA/2 GADA, IA-2A 354 - SU treatment denotes complete withdrawal of insulin therapy unless specified. Login to comment
78 Finally, a patient carrying the unreported ABCC8/A355T (c.1063G>A; nd-NA/2) variant inherited the mutation from his mother, who was diagnosed with gestational diabetes at the age of 26 years. Login to comment
91 A355T GD 26 years 48 years Family nd-NA/2 A355T PNDM/MDI 71 days 21 years INS I. II. L213P PNDM/MDI 51 days 44 years INS L213P PNDM/MDI 40 days 14 years INS Family nd-PR/2 I. II. Family nd-PD/2 L213P PNDM/MDI 3 days 11 years INS I. II. Fig. 1 Pedigrees of four families with mutations in ABCC8; from top to bottom: mutation, phenotype, age at presentation/diagnosis of diabetes, current age and initial therapy for diabetes. Login to comment
101 In contrast, we cannot explain at this time the extremely different phenotypes we observed in the carriers of the mutation ABCC8/A355T, who show either PNDM/MDI or gestational diabetes. Login to comment
103 Because the patient with ABCC8/A355T also has a liver-related and haematologic phenotype, it is conceivable that he may carry a mutation in another locus that impacts on glucose metabolism. Login to comment
104 Functional studies are definitely needed to firmly establish the impact of ABCC8/A355T on insulin secretion. Login to comment
116 Conversely, we think that the nine patients in group 1 who had no disease-causing mutation identified, and possibly the patient carrying the ABCC8/A355T mutation, who showed clinical features not associated with mutations to KATP channel genes, are likely to carry a mutation in a locus that has not, as yet, been found. Login to comment