A novel homozygous mutation of the nicotinamide nucleotide transhydrogenase gene in a Japanese patient with familial glucocorticoid deficiency
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Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by primary hypocortisolism and normal mineralocorticoid production. Recently, <i>NNT</i> encoding the nicotinamide nucleotide transhydrogenase has been identified as a causative gene for FGD. Thus, we examined <i>NNT</i> in six Japanese FGD patients with no recognizable mutation in the previously known four responsible genes for FGD (<i>MC2R</i>, <i>MRAP</i>, <i>STAR</i>, and <i>MCM4</i>), and identified a novel homozygous substitution (c.644T>C; p.Phe215Ser) in a single 17.5-year-old boy. His parents were heterozygous for this mutation. This substitution was absent from 120 Japanese control subjects and was not registered in public databases including JSNP Database. The phenylalanine residue at the 215th codon was evolutionally conserved, and the p.Phe215Ser was assessed to be a pathologic mutation by <i>in silico</i> protein function analyses. The results, in conjunction with the previous data, imply that <i>NNT</i> mutations account for 5-10% of FGD patients, and that underlying factor(s) still remains to be clarified in a substantial fraction of FGD patients.
- Endocrine Journal
Endocrine Journal 60(7), 855-859, 2013-07-01
The Japan Endocrine Society