Caused by a homozygous frameshift mutation, 2067insC, in the GLIS3 gene predicted to lead to a frameshift and a truncated protein (625FS703STOP), altering the C-terminal proline-rich domain (PMID:16715098).
Taha et al. (2003) described a consanguineous Saudi Arabian family in which 2 of 4 sibs had a syndrome of minor facial anomalies, proportionate intrauterine growth retardation, neonatal nonimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and ... Taha et al. (2003) described a consanguineous Saudi Arabian family in which 2 of 4 sibs had a syndrome of minor facial anomalies, proportionate intrauterine growth retardation, neonatal nonimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and polycystic kidneys. The liver disease progressed to hepatic fibrosis. The renal disease was characterized by large kidneys and multiple small cysts with deficient corticomedullary junction differentiation and normal kidney function. The phenotype observed in the 2 sibs was identical. Although a combination of liver, kidney, and pancreatic involvement had been described in renal-hepatic-pancreatic syndrome (see 263200), the coexistence of neonatal diabetes mellitus, congenital hypothyroidism, and glaucoma in the sibs suggested the possibility that this combination describes a distinct autosomal recessive syndrome. Senee et al. (2006) studied the original NDH family described by Taha et al. (2003) as well as a second Saudi Arabian family and a consanguineous French family. They reported that a third child was born in this family, bearing the same clinical features with the exception of cystic kidney disease. All 3 affected individuals died at 16 months of age or younger, from pneumonia and respiratory failure or sepsis. In the second Saudi Arabian family, liver and kidneys were normal, and in the 2 affected individuals in the third family, liver, kidneys, and eyes were normal.
Senee et al. (2006) described mutations in the GLIS3 gene (see 610192.0001) in the original NDH family described by Taha et al. (2003) and also in a second Saudi Arabian family and a French family.