Details of Disease

General Information of Disease (ID: DISEB8Q0)

• Disease Name: Monogenic diabetes
• Synonyms: monogenic diabetes; rare genetic diabetes mellitus
• Definition: Diabetes mellitus that is caused by mutations in a single gene.
• Disease Hierarchy:
  DISIUHAP: Type-1/2 diabetes
  DISO5FAY: Inborn error of metabolism
  DISEB8Q0: Monogenic diabetes
• Disease Identifiers:
  MONDO ID: MONDO_0015967
  UMLS CUI: C3888631
  MedGen ID: 1392102
  Orphanet ID: 183625

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BLK	TTNDSC3	Refuted	Autosomal dominant	[1]
G6PC2	TT7EV4P	Limited	Genetic Variation	[2]
INSR	TTCBFJO	Limited	Biomarker	[3]
PDX1	TT8SGZK	Limited	Genetic Variation	[4]
PDX1	TT8SGZK	Moderate	Autosomal dominant	[1]
ABCC8	TTP835K	Strong	Genetic Variation	[5]
INS	TTZOPHG	Strong	Genetic Variation	[6]
KCNJ11	TT329V4	Strong	Genetic Variation	[7]
MC4R	TTD0CIQ	Strong	CausalMutation	[8]
SLC19A2	TT2A1DZ	Strong	Genetic Variation	[9]
GCK	TTDLNGZ	Definitive	Autosomal dominant	[1]
HNF1A	TT01M3K	Definitive	Autosomal dominant	[1]
HNF1A	TT01M3K	Definitive	Genetic Variation	[10]
HNF4A	TT2F3CD	Definitive	Autosomal dominant	[1]
INS	TTZOPHG	Definitive	Autosomal recessive	[1]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCC8	DTI58LU	Definitive	Semidominant	[1]
KCNJ11	DTGZICY	Definitive	Autosomal dominant	[1]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BLK	OT1EB8MT	Refuted	Autosomal dominant	[1]
KLF11	OTKVQDJD	Refuted	Autosomal dominant	[1]
APPL1	OT8VR95S	Limited	Autosomal dominant	[1]
GATA6	OTO2BC0F	Limited	Biomarker	[11]
GCKR	OTSIWXGG	Limited	Genetic Variation	[2]
GLIS3	OTBC960E	Disputed	Biomarker	[12]
LMNA	OT3SG7ZR	moderate	CausalMutation	[13]
NEUROD1	OTZQ7QJ2	Moderate	Autosomal recessive	[1]
PDX1	OTX1DKRA	Moderate	Autosomal dominant	[1]
BSCL2	OT73V6Y4	Strong	CausalMutation	[14]
HNF1B	OTSYIC3T	Strong	Biomarker	[15]
INS-IGF2	OTZR74BO	Strong	Genetic Variation	[16]
ABCC8	OTCWQ54I	Definitive	Semidominant	[1]
GCK	OTR3Q0NN	Definitive	Autosomal dominant	[1]
HNF1A	OT9DOUKL	Definitive	Autosomal dominant	[1]
HNF4A	OTY1TOAB	Definitive	Autosomal dominant	[1]
INS	OTZ85PDU	Definitive	Autosomal recessive	[1]
KCNJ11	OTPUUELV	Definitive	Autosomal dominant	[1]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Genetic variability of GCKR alters lipid profiles in children with monogenic and autoimmune diabetes.Exp Clin Endocrinol Diabetes. 2014 Oct;122(9):503-9. doi: 10.1055/s-0034-1375648. Epub 2014 Jun 11.
• [3] Systematic Population Screening, Using Biomarkers and Genetic Testing, Identifies 2.5% of the U.K. Pediatric Diabetes Population With Monogenic Diabetes.Diabetes Care. 2016 Nov;39(11):1879-1888. doi: 10.2337/dc16-0645. Epub 2016 Jun 6.
• [4] PDX1 -MODY and dorsal pancreatic agenesis: New phenotype of a rare disease.Clin Genet. 2018 Feb;93(2):382-386. doi: 10.1111/cge.13044. Epub 2017 Jul 19.
• [5] Phenotypic variability in two siblings with monogenic diabetes due to the same ABCC8 gene mutation.Pediatr Diabetes. 2019 Jun;20(4):482-485. doi: 10.1111/pedi.12826. Epub 2019 Apr 2.
• [6] Clinical, Genetic, and Biochemical Characteristics of Early-Onset Diabetes in the Finnish Population.J Clin Endocrinol Metab. 2016 Aug;101(8):3018-26. doi: 10.1210/jc.2015-4296. Epub 2016 May 11.
• [7] Congenital forms of diabetes: the beta-cell and beyond.Curr Opin Genet Dev. 2018 Jun;50:25-34. doi: 10.1016/j.gde.2018.01.005. Epub 2018 Feb 16.
• [8] Prevalence and phenotypic characterization of MC4R variants in a large pediatric cohort.Int J Obes (Lond). 2017 Jan;41(1):13-22. doi: 10.1038/ijo.2016.161. Epub 2016 Sep 22.
• [9] Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of <5 years in the Iranian population.Diabet Med. 2019 Dec;36(12):1694-1702. doi: 10.1111/dme.14071. Epub 2019 Jul 25.
• [10] A decision algorithm to identify patients with high probability of monogenic diabetes due to HNF1A mutations.Endocrine. 2019 Apr;64(1):75-81. doi: 10.1007/s12020-019-01863-7. Epub 2019 Feb 18.
• [11] Two novel GATA6 mutations cause childhood-onset diabetes mellitus, pancreas malformation and congenital heart disease.Horm Res Paediatr. 2013;79(4):250-6. doi: 10.1159/000348844. Epub 2013 Apr 26.
• [12] Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes.Endocr Rev. 2016 Jun;37(3):190-222. doi: 10.1210/er.2015-1116. Epub 2016 Apr 1.
• [13] Homozygous lamin A/C familial lipodystrophy R482Q mutation in autosomal recessive Emery Dreifuss muscular dystrophy.Neuromuscul Disord. 2013 Mar;23(3):265-8. doi: 10.1016/j.nmd.2012.11.011. Epub 2013 Jan 11.
• [14] A Patient with Congenital Generalized Lipodystrophy Due To a Novel Mutation in BSCL2: Indications for Secondary Mitochondrial Dysfunction.JIMD Rep. 2012;4:47-54. doi: 10.1007/8904_2011_86. Epub 2011 Nov 4.
• [15] A cross-sectional study of patients referred for HNF1B-MODY genetic testing due to cystic kidneys and diabetes.Pediatr Diabetes. 2020 May;21(3):422-430. doi: 10.1111/pedi.12959. Epub 2020 Jan 29.
• [16] INS-gene mutations: from genetics and beta cell biology to clinical disease.Mol Aspects Med. 2015 Apr;42:3-18. doi: 10.1016/j.mam.2014.12.001. Epub 2014 Dec 24.