Mody6 E11.-

MODY is the acronym for "Maturity-onset Diabetes of the Young" and describes a group of autosomal-dominantly inherited, genetically heterogeneous, not always insulin-dependent forms of diabetes. The MODY forms of diabetes are caused by various disorders of beta cell function in the pancreas. The body weight of MODY patients is usually normal. Neither are any of the autoimmune phenomena characteristic of type 1 diabetes observed. Rare are other associated organ dysplasias (eyes, pancreas, intestine).

<1% of MODY cases

In the rare MODY 6 variant, mutations are present in the NEUROD1 gene, a gene that codes for a transcription factor that regulates the expression of the INS gene by binding to the promoter region of the insulin gene.

Clinically MODY 6 shows a very variable symptomatology partly associated with obesity. A pathologically decreased insulin production is in the foreground. The inheritance is autosomal dominant, the penetrance with approx. 80-90% is very high.

To avoid late complications, the therapeutic goal is to achieve normal glycaemia with as normal an HbA1c value as possible. Insulin therapy is recommended for MODY 6.

Indication for the detection of MODY 5 gene mutation:

• Manifestation age in early adolescence
• no GAD and/or IA2 antibodies (exclusion of type 1 diabetes)
• Positive family history, autosomal dominant inheritance
• Diabetes without obesity
• Progressive hyperglycaemia in old age
• No insulin resistance
• Pancreatic aplasia with neonatal diabetes
• An examination of the NEUROD1 gene is useful if the examination of the genes HNF1A, HNF4A and GCK was inconspicuous in patients with clinically severe, especially MODY diabetes.

1. Fajans S et al (2019) Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. New Eng J Med 345: 971-980

2. Guo Z et al (2014) In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model. Cell Stem Cell 14: 188-202.

3. Lee JE et al (1995) Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein. Science 268: 836-844.

4. Liu M et al (2000) Essential role of BETA2/NeuroD1 in development of the vestibular and auditory systems. Genes Dev14: 2839-2854.

5. Malecki M et al (1999) Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nature Genet 23: 323-328.

6. Szopa M et al (2016) A family with the Arg103Pro mutation in the NEUROD1 gene detected by next-generation sequencing - Clinical characteristics of mutation carriers. Eur J Med gene 59:75-79.