Maturity-Onset Diabetes Of The Young, Type 11

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

INS, PDX1, HNF1A, GCK, NEUROD1, HNF4A, KCNJ11, PAX4, KLF11, BLK, HNF1B, CEL, APPL1, ABCC8, TGM2, MAFA, CERKL, TCF7, ADA, CRP, GAD1, INSR, HK1, PDHX, SLC2A1, GCG, GCKR, PLCG1, PSMD9, RFX6

INS, PDX1, HNF1A, GCK, NEUROD1, HNF4A, KCNJ11, PAX4, KLF11, BLK, HNF1B, CEL, APPL1, ABCC8, TGM2, MAFA, CERKL, TCF7, ADA, CRP, GAD1, INSR, HK1, PDHX, SLC2A1, GCG, GCKR, PLCG1, PSMD9, RFX6, GLP1R, APOM, FOXA2, NEUROG3, PPP1R3B, EBI3, EIF2AK3, FUBP1, SLC19A2, FANCD2, IL18R1, APRT, PASK, ECB2, TNDM, WFS1, ASIP, NR2F2, SACM1L, SLC30A10, APOC3, APOB, ZGLP1, GGTLC4P, GGT2, GGTLC3, GGTLC5P, ALB, SLC30A8, PTPN22, MED25, EHMT1, NEUROD4, FXYD2, RAB14, CYB5R4, ATM, SCT, BAD, KCNJ1, ISL1, CREBBP, IL6R, IAPP, ONECUT1, EGF, GPD1, GIP, GHRH, GGT1, FABP1, GATA6, FOLR2, FOLR1, FBP1, KCNC4, CD36, SERPINA7, LEPR, BRAF, SLC2A2, FBN2, MAP4K2, PTPRN, PSEN1, PRKG1, PPARA, PCK1, PCBD1, AKT2, NKX6-1, BRCA2, MTNR1B, MFAP1, LOC102723407

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A number sign (#) is used with this entry because this form of maturity-onset diabetes of the young (MODY11) is caused by heterozygous mutation in the BLK gene (191305) on chromosome 8p23-p22.

For a phenotypic description and a discussion of genetic heterogeneity of MODY, see 606391.

Mapping

Kim et al. (2004) performed a genomewide scan of 21 extended United States families segregating autosomal dominant maturity-onset diabetes of the young (MODY) not caused by known MODY genes. They found significant linkage to chromosome 8p23 in 6 of the families, with a heterogeneity-adjusted lod score of 3.37 at D8S1130 and nonparametric lod of 3.66 at D8S265 (p = 2 x 10(-5)). Haplotype analysis defined an approximately 2.7-Mb critical interval between markers D8S1706 and D8S1721. Kim et al. (2004) noted that there was a higher prevalence of obesity in individuals with diabetes linked to 8p23 than in diabetic individuals with MODY linked to other loci.

Molecular Genetics

Borowiec et al. (2009) resequenced all transcripts described in the linked 2.5-Mb interval on chromosome 8p23 in 2 diabetic members from each of 6 MODY families supporting linkage at this location and identified 5 sequence differences that cosegregated with diabetes and had a frequency of less than 1% in the general population. The 5 mutations were all within a 100-kb stretch of genomic sequence corresponding to the BLK gene (191305). Three mutations (191305.0001-191305.0003) occurred as a haplotype in 1 family (family 'F8'). Noting that the penetrance of the F8 haplotype was 0.33 (2 affected out of 6) among carriers with a body mass index (BMI) less than 28 compared to 0.89 (8 affected out of 9) among carriers with a BMI greater than or equal to 28, Borowiec et al. (2009) suggested that the diabetogenic environment conferred by an increased body weight might be necessary for translation of the beta-cell abnormalities caused by the F8 haplotype into diabetes.