Clinical characteristics of mutation carriers in a large family with glucokinase diabetes (MODY2).

Abstract

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 +/- 390 grams, 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.

• Authors: N Shehadeh, D Bakri, P R Njølstad, R Gershoni-Baruch
• Journal: Diabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 22 Issue 8 Pg. 994-8 (Aug 2005) ISSN: 0742-3071 [Print] England
• PMID: 16026363 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Glucokinase

Topics

• Adolescent
• Adult
• Aged
• Blood Glucose (analysis)
• Body Mass Index
• Child
• Child, Preschool
• Diabetes Mellitus (genetics)
• Female
• Glucokinase (genetics)
• Glucose Tolerance Test
• Heterozygote
• Humans
• Infant
• Male
• Middle Aged
• Mutation (genetics)