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tRNA methyltransferase homologue gene TRMT 10A mutation in young adult‐onset diabetes with intellectual disability, microcephaly and epilepsy
Author(s) -
Yew T. W.,
McCreight L.,
Colclough K.,
Ellard S.,
Pearson E. R.
Publication year - 2016
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.13024
Subject(s) - microcephaly , intellectual disability , medicine , epilepsy , sanger sequencing , maturity onset diabetes of the young , diabetes mellitus , nonsense mutation , genetics , mutation , pediatrics , gene , endocrinology , missense mutation , type 2 diabetes , psychiatry , biology
Background A syndrome of young‐onset diabetes mellitus associated with microcephaly, epilepsy and intellectual disability caused by mutations in the tRNA methyltransferase 10 homologue A ( TRMT 10A ) gene has recently been described. Case report We report two siblings from the fourth family reported to have diabetes mellitus as a result of a TRMT 10A mutation. A homozygous nonsense mutation p.Glu27Ter in TRMT 10A was identified using targeted next‐generation sequencing and confirmed by PCR /Sanger sequencing. Diabetes was diagnosed while the subjects were in their 20s and was characterized by insulin resistance. Epilepsy and intellectual disability were features in common. Mild microcephaly was present at birth but their final head circumferences were normal. Conclusion Our report provides independent confirmation of the role of TRMT 10A mutations in this syndrome and expands its phenotypic description. TRMT 10A sequencing should be considered in children or adults with young‐onset diabetes who have a history of intellectual disability, microcephaly and epilepsy. This report also shows the advantages of using a targeted panel to identify previously unsuspected monogenic diabetes among young‐onset non‐insulin‐dependent diabetes in the absence of obesity and autoimmunity.