Pathogenicity of a glucokinase gene mutation and description of its clinical phenotype.

Glucokinase gene (GCK) mutations comprise approximately 10% of cases of maturity-onset diabetes of the young (MODY). Over 800 different mutations in GCK have been reported in the Human Gene Mutation Database, the vast majority of which result in MODY type 2. The missense mutation p.Leu122Val is listed in that database as "disease-causing;" however, the National Center for Biotechnology Information ClinVar database (Variation ID 585919) reports that this mutation is of "uncertain significance." Both databases reference the same Italian pediatric patient reported by Massa et al in 2001, but no phenotypic description of the patient is included in the original article. We report a pedigree of three patients over two generations affected with GCK mutation c.364C > G (p.Leu122Val) to support the clinical significance of this mutation and to provide the first phenotypic description of patients with this particular mutation.