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Clinical characteristics of mutation carriers in a large family with glucokinase diabetes (MODY2)
Author(s) -
Shehadeh N.,
Bakri D.,
Njølstad P. R.,
GershoniBaruch R.
Publication year - 2005
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2005.01555.x
Subject(s) - medicine , glucokinase , diabetes mellitus , mutation , endocrinology , genetics , gene , biology
Aims To investigate the prevalence and clinical characteristics of heterozygotes of the glucokinase gene mutations G264S and IVS8+2 in the extended pedigree of two patients with permanent neonatal diabetes as a result of glucokinase deficiency (IVS8+2 homozygosity and IVS8+2/G264S compound heterozygosity). Methods Eighty‐eight first, second and third degree family members of the two patients with permanent neonatal diabetes were genotyped. Clinical, laboratory and historical data were collected via chart reviews. Results Thirty‐one IVS8+2 and three G264S heterozygotes were identified. Of these, 18/34 (52.9%) had diabetes and 9/34 (26.5%) impaired fasting glucose (IFG), compared with 1/54 (1.9%) with diabetes and 2/54 (3.7%) with IFG in the non‐carrier group. Odds ratio for heterozygotes was 70.4 (95% CI 16.9–293.5 and P < 0.001). Mean body mass index of heterozygotes (> 18 years of age) who had diabetes was 27.1 ± 2.66, compared with 23.18 ± 4.72 for heterozygotes with normal glucose levels ( P < 0.05). While none of the non‐carrier women had gestational diabetes, eight of the 10 heterozygotes developed gestational diabetes. Inheritance of a glucokinase mutation by the fetus from a carrier mother resulted in a significant reduction in birthweight (3600 ± 570 vs. 2970 ± 390grams, P < 0.05). Conclusions These data support the association between carriage of GCK gene mutations, G264S and IVS8+2, and the development of diabetes, impaired fasting glucose and reduced birthweight. Moreover, in heterozygotes, a clear correlation between body mass index and the development of diabetes was observed. These findings underline the need for surveillance and prevention in individuals at risk.