Is LMNB1 a susceptibility gene for neural tube defects in humans?. Issue 6 (3rd June 2013)

• Record Type: Journal Article
• Authors: Robinson, Alexis; Partridge, Darren; Malhas, Ashraf; De, Sandra C.P.; Gustavsson, Peter; Thompson, Dominic N.; Vaux, David J.; Copp, Andrew J.; Stanier, Philip; Bassuk, Alexander G.; Greene, Nicholas D.E.
• Is Part Of: Birth defects research. Volume 97:Issue 6(2013:Jun.)
• Page Start: 398
• Page End: 402
• Publication Date: 2013-06-03
• Subjects: Teratology -- Periodicals; Abnormalities, Human -- Research -- Periodicals; Abnormalities, Human -- Periodicals; 616.043
• DOI: 10.1002/bdra.23141
• Languages: English
• ISSNs: 1542-0752

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bdra23141-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Lamins are intermediate filament proteins that form a major component of the nuclear lamina, a protein complex at the surface of the inner nuclear membrane. Numerous clinically diverse conditions, termed laminopathies, have been found to result from mutation of <italic>LMNA</italic>. In contrast, coding or loss of function mutations of <italic>LMNB1</italic>, encoding lamin B1, have not been identified in human disease. In mice, polymorphism in <italic>Lmnb1</italic> has been shown to modify risk of neural tube defects (NTDs), malformations of the central nervous system that result from incomplete closure of the neural folds.</p> </sec> <sec id="bdra23141-sec-0002" sec-type="section"> <title>METHODS</title> <p>Mutation analysis by DNA sequencing was performed on all exons of <italic>LMNB1</italic> in 239 samples from patients with NTDs from the United Kingdom, Sweden, and United States. Possible functional effects of missense variants were analyzed by bioinformatics prediction and fluorescence in photobleaching.</p> </sec> <sec id="bdra23141-sec-0003" sec-type="section"> <title>RESULTS</title> <p>In NTD patients, we identified two unique missense variants that were predicted to disrupt protein structure/function and represent putative contributory mutations. Fluorescence loss in photobleaching analysis showed that the A436T variant compromised stability of lamin B1 interaction within the lamina.</p> </sec> <sec id="bdra23141-sec-0004" sec-type="section"> <title>CONCLUSION</title> <p>The genetic basis of human NTDs appears highly heterogenous with possible involvement of multiple predisposing genes. We hypothesize that rare variants of <italic>LMNB1</italic> may contribute to susceptibility to NTDs. <italic>Birth Defects Research (Part A) 97:398–402, 2013</italic>. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>