Back to Search
Start Over
Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: Phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1beta gene due to germline mosaicism.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2004 Jun; Vol. 89 (6), pp. 2905-8. - Publication Year :
- 2004
-
Abstract
- Mutations in the gene coding for hepatocyte nuclear factor-1beta (HNF-1beta) have been known to cause a form of maturity-onset diabetes of the young (MODY5), which is usually characterized by dominantly inherited adolescence-onset diabetes mellitus associated with renal cysts. This report, however, describes recurrence of a novel missense mutation in the HNF-1beta gene, S148W (C443G), in two sibs, one with neonatal diabetes mellitus and the other with neonatal polycystic, dysplastic kidneys leading to early renal failure. The former patient had only a few small renal cysts with normal renal functions, and the latter had only a transient episode of hyperglycemia, which resolved spontaneously. Interestingly, both parents were clinically unaffected, and PCR restriction fragment length polymorphism analysis showed that the mother was a low-level mosaic of normal and mutant HNF-1beta, which suggested that the recurrence was caused by germline mosaicism. This is the first report of permanent neonatal diabetes mellitus caused by a mutation of the HNF-1beta gene as well as the first report of germline mosaicism of this gene. In addition, the two cases described here show that additional factors, genetic or environmental, can have a significant influence on the phenotypic expression of HNF-1beta mutations.
- Subjects :
- Child
Child, Preschool
DNA Mutational Analysis
Diabetes Mellitus, Type 2 complications
Female
Genotype
Hepatocyte Nuclear Factor 1-beta
Humans
Infant, Newborn
Male
Mosaicism
Mutation, Missense
Phenotype
Polycystic Kidney Diseases complications
DNA-Binding Proteins genetics
Diabetes Mellitus, Type 2 genetics
Germ-Line Mutation
Infant, Newborn, Diseases genetics
Polycystic Kidney Diseases genetics
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0021-972X
- Volume :
- 89
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 15181075
- Full Text :
- https://doi.org/10.1210/jc.2003-031828