Homozygous mutations in the GLIS3 gene have been typically associated with Neonatal Diabetes and Congenital Hypothyroidism (CH) in a syndrome called NDH.
Loss of GLIS3 function in humans and mice leads to the development of several pathologies, including neonatal diabetes and congenital hypothyroidism, polycystic kidney disease, and infertility.
Gene variants have been reported to be associated with congenital hypothyroidism (CH), the purpose of this study was to analyze the mutation spectrum and prevalence of 12 known causative genes (TSHR, PAX8, NKX2.1, NKX2.5, FOXE1, DUOX2, TG, TPO, GLIS3, NIS, SLC26A4 and DEHAL1) in CH in China.
Mutations in the GLI-similar 3 (GLIS3) gene encoding the transcription factor GLIS3 are a rare cause of neonatal diabetes and congenital hypothyroidism with 12 reported patients to date.
The association of permanent neonatal diabetes and congenital hypothyroidism was first reported in 2003 and subsequently led to the identification GLIS3 as the mutation responsible for this presentation.
Deficiency in Krüppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in humans is associated with the development of congenital hypothyroidism.
The Glis3 mutant mice have been characterized for their propensity to develop congenital hypothyroidism, polycystic kidney disease, and some types of cancer.
We also report the first case of a recessive GLIS3 mutation causing neonatal diabetes and congenital hypothyroidism in a child from a non-consanguineous pedigree, highlighting the importance of molecular genetic testing in any patient with this phenotype.