title: 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.
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.
authors.affiliation: Department of Pediatrics, Kyoto University Hospital, Kyoto 606-8507, Japan. yorif@kuhp.kyoto-u.ac.jp
authors.forename: Tohru
authors.initials: T
authors.lastname: Yorifuji
authors.forename: Keiji
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Mitsukazu
authors.initials: M
authors.lastname: Mamada
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Imai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kawai
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nishi
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Shishido
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
mesh_terms: D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics*; D008297:Male; D009030:Mosaicism; D020125:Mutation, Missense; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000150:complications / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C496495:HNF1B protein, human; D014157:Transcription Factors; D051539:Hepatocyte Nuclear Factor 1-beta