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Mutation in HNF4A associated with an increase in birthweight and macrosomia

03.04.2007
A mutation in one gene HNF4A, associated with diabetes in the young, has been shown to be associated with an average increase in birthweight of 790g.

In the current issue of PLoS Medicine Andrew Hattersley and colleagues from the Peninsular Medical School, report the findings from a study of 108 individuals from15 families where the mutation was present. Overall more than half of the babies who carried the mutation were defined as macrosomic compared with 13% of those with no mutations.

Macrosomia (birthweight more than 4000g) is associated with complications for both mothers and babies; one cause of macrosomia is diabetes in the mother. The particular type of diabetes investigated in this study is known as maturity-onset diabetes of the young (MODY) genes; two of the genes known to be involved in this disease are HNF4A and HNF1A/TCF1 both of which have a key role in the regulation of the secretion of insulin by the pancreas.

In addition to increased birthweight the researchers also found that low blood-sugar levels at birth were also more common in babies carrying the HNF4A mutation as
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compared to those who did not. In mice who lacked the equivalent mouse gene (Hnf4a) the researchers were able to show that there was high insulin during development and low blood sugar at birth.

Although this study is in patients with an unusual mutation, these results have wider implications as they establish that HNF4A is important in determining birthweight. However, the mechanism by which the same mutation also causes diabetes (ie with decreased insulin) in later life remains to be determined in view of the increased insulin shown to be present at birth that causes the low glucose. Nonetheless, the authors conclude that “in addition to maternal factors, paternal factors (including history of diabetes) should be considered when assessing macrosomia risk.” A related perspective by Benjamin Glaser from the Hadassah-Hebrew University Medical Center, discusses the paper’s implications further

Citation: Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, et al. (2007) Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 4(4): e118.

CONTACT:
Andrew T Hattersley
Peninsula Medical School
Institute of Biomedical Sciences
Barrack Road
Exeter, Devon EX2 5DW
United Kingdom
+44 1392 406806
andrew.hattersley@pms.ac.uk

Andrew Hyde | alfa
Further information:
http://www.plosmedicine.org
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040118

Further reports about: Diabetes HNF4A Insulin birthweight macrosomia

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