Detection and characterization of two novel mutations in the HNF4A gene in maturity-onset diabetes of the young type 1 in two Japanese families

Makoto Fujiwara, Noriyuki Namba, Kohji Miura, Taichi Kitaoka, Haruhiko Hirai, Hiroki Kondou, Tsunesuke Shimotsuji, Chikahiko Numakura, Keiichi Ozono
Hormone Research in Pædiatrics 2013, 79 (4): 220-6

BACKGROUND: Maturity-onset diabetes of the young (MODY) is a subgroup of monogenic diabetes mellitus, of which MODY1, caused by HNF4A mutations, accounts for only 5% or less and has been rarely reported in East Asian countries. Here we report two novel HNF4A mutations in two Japanese families with MODY1.

METHODS: Proband 1 is an 8-year-old girl and proband 2 is a 14-year-old girl. Both were nonobese, demonstrated elevated HbA1c and negative serum anti-glutamic acid decarboxylase antibodies, and had a family history of diabetes. We directly sequenced HNF4A and performed functional analysis of the detected missense mutation.

RESULTS: Proband 1 had a heterozygous missense mutation, c.824A>G (p.Asn275Ser). Luciferase assay demonstrated a significant reduction in transcriptional activity. A heterozygous frame shift mutation, c.692-695delAGGA (p.Lys231ThrfsX5), was detected in proband 2. Affected family members shared the same mutations, showing high penetrance. Both mutations reside in the HNF4α dimerization domain and the corresponding amino acids are well conserved between species.

CONCLUSIONS: These two mutations are most likely the cause of MODY1 in these families. Considering the effectiveness of sulfonylureas, it is important to correctly diagnose MODY1.


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"