| # | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
|---|
| 1 | not provided | 2 | not provided | not provided | clinical testing |
PubMed (2)
|
| 2 | not provided | 4 | not provided | not provided | clinical testing |
PubMed (2)
|
| 3 | not provided | 6 | not provided | not provided | clinical testing |
PubMed (2)
|
Description
two sisters suffered from adult-onset insulinomatosis
4 further heterozygous relatives showed a MODY-like form of diabetes mellitus
Six other relatives carried the variant in heterozygous form, but no information was available on their blood glucose status. Four of these are childre, too young to develop symptoms (3-7 years of age).
Description
Using exome sequencing (conformation using Sanger Sequencing), we detected a novel, heterozygous missense variant, c.170C>G p.(Thr57Arg), in MAFA’s highly conserved transactivation domain in two sisters who suffer from adult-onset familial insulinomatosis. Furthermore, mild hyperglycemia was observed in six additional, heterozygote family members, indicating that not only insulinomatosis but also MODY-like symptoms co-segregate with p.Thr57Arg. Details on methods, family and clinical details can be found in PMID: 35406570. In vitro expression studies replacing Thr57 have already been performed by Han et al., demonstrating a phosphorylation defect with impairment of transactivation activity and degradation (PMID: 17682063). The MAFA variant, p.Ser64Phe, is located in the same domain, impairs the same phosphorylation cascade, and results in the same symptoms (PMID: 29339498). Therfore, we classified the variant NM_201589.4(MAFA):c.170C>G as pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | 2 | not provided | 1 | not provided |
| 2 | germline | yes | not provided | not provided | not provided | | 4 | not provided | 1 | not provided |
| 3 | germline | unknown | not provided | not provided | not provided | | 6 | not provided | 1 | not provided |
