ABCMdb

PMID: 17635943

Suzuki S, Makita Y, Mukai T, Matsuo K, Ueda O, Fujieda K
Molecular basis of neonatal diabetes in Japanese patients.
J Clin Endocrinol Metab. 2007 Oct;92(10):3979-85. Epub 2007 Jul 17., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCC8 p.Ala90Val ABCC8 p.Asn1122Asp Five mutations were novel: two (p.A174G and p.C166Y) in KCNJ11, two (p.A90V and p.N1122D) in ABCC8, and one (p.P367L) in FOXP3. Login to comment 56 ABCC8 p.Ala90Val ABCC8 p.Ala90Val ABCC8 p.Asn1122Asp ABCC8 p.Asn1122Asp The novel mutations were the substitution of alanine by valine at codon 90 (c.269CϾT, p.A90V) and the substitution of asparagine by aspartate at codon 1122 (c.3364AϾG, p.N1122D). Login to comment 79 ABCC8 p.Ala90Val ABCC8 p.Asn1122Asp They exhibited hyperglycemia, leading to fever and dehydration in the patient with the A90V mutation and severe DKA, resulting in seizure in the patient with the N1122D mutation. Login to comment 88 ABCC8 p.Ala90Val ABCC8 p.Asn1122Asp The patients with R50G, C166Y, R201C, or R201H in the KCNJ11 and A90V mutations or N1122D in the ABCC8 mutation have been treated with insulin since diagnosis of diabetes. Login to comment 98 ABCC8 p.Ala90Val ABCC8 p.Asn1122Asp Sex Year of birth Age at last visit (yr) Diabetes form Genetic defect Age at onset of diabetes (d) Age at remission (d) Remark 1 M 2001 0.7 TNDM pUPD(6) 10 161 Macroglossia at onset 2 M 2002 2.8 TNDM pUPD(6) 9 104 Macroglossia at onset 3 M 2005 0.6 TNDM pUPD(6) 4 62 4 F 2002 0.3 TNDM pUPD(6) 11 62 Macroglossia at onset 5 F 2003 2.0 TNDM pUPD(6) 0 91 Extremely premature baby 6 F 2005 0.4 TNDM pUPD(6) 8 39 7 F 2000 5.4 TNDM pUPD(6) 1 26 Prominent forehead 8 M 2004 0.7 TNDM 6q24 duplication 6 16 9 M 2002 2.5 TNDM 6q24 duplication 2 173 Macroglossia at onset 10 M 2004 0.9 TNDM 6q24 duplication 8 35 Macroglossia at onset 11 F 1994 11.2 TNDM 6q24 duplication 6 246 Recurrence at 10 yr of age (38) 12 M 2003 1.3 TNDM KCNJ11 (p.R50Q) 9 307 13 M 1986 14.6 TNDM KCNJ11 (p.A174G) 17 307 Recurrence at 13 yr of age 14 M 2004 2.0 PNDM KCNJ11 (p.R201H) 33 15 F 2004 0.5 PNDMa KCNJ11 (p.R201H) 54 16 M 2004 2.0 PNDM KCNJ11 (p.R201H) 42 17 M 2006 0.3 PNDMa KCNJ11 (p.R201H) 54 18 F 2000 5.0 PNDM KCNJ11 (p.R201C) 49 19 M 1997 8.3 PNDM KCNJ11 (p.R50G) 115 DEND syndrome, arthroglyposis 20 F 2003 3.1 PNDM KCNJ11 (p.C166Y) 98 DEND syndrome, arthroglyposis, prominent forehead, ptosis 21 M 2004 1.7 PNDM ABCC8 (p.A90V) 40 22 M 2006 0.3 PNDMa ABCC8 (p.N1122D) 50 23 M 2001 0.3 PNDM FOXP3 (p.P367 liter) 8 Died at 4 months of age 24 M 2000 3.6 TNDM Unknown 10 27 Extremely premature baby 25 M 2001 0.2 TNDM Unknown 11 25 Extremely premature baby 26 M 2005 0.2 TNDM Unknown 13 60 Macroglossia at onset 27 M 2003 1.9 PNDM Unknown (no IPF1 mutation) 9 Pancreatic agenesis 28 M 2002 3.4 PNDM Unknownb 42 29 M 2002 1.2 PNDM Unknown 18 Congenital deafness, cataract, mental retardation, liver dysfunction 30 M 1991 13.9 PNDM Unknown 55 Severe developmental delay 31 F 2002 3.0 PNDM Unknown 93 Congenital cataract, severe developmental delay F, Female; M, male. Login to comment 126 ABCC8 p.Asn1122Asp *, Classification of diabetes of two patients with R201H in the KCNJ11 mutation, and the patient with N1122D in the ABCC8 mutation may remain undetermined because of the short follow-up period. Login to comment 159 ABCC8 p.Ala90Val ABCC8 p.Asn1122Asp The novel A90V and N1122D mutations are located in TMD0 and TMD2, respectively. Login to comment 161 ABCC8 p.Phe132Leu ABCC8 p.His1023Tyr The reported mutations F132L (4) and H1023Y (5) are located in TMD0 and TMD2, respectively, and functional studies confirmed that these mutations reduced ATP sensitivity. Login to comment 162 ABCC8 p.Ala90Val ABCC8 p.Asn1122Asp Thus, the functional consequence of the novel mutations A90V and N1122D is likely to overactivate beta-cell ATP-sensitive Kϩ channels. Login to comment