Recurrent ACTG2 gene variation in African degenerative visceral leiomyopathy.
INTRODUCTION
Visceral myopathies remain difficult and frustrating clinical entities, a distinctive form of acquired degenerative visceral myopathy, African degenerative leiomyopathy, a myogenic functional intestinal obstruction without aganglionosis which affects smooth muscle of the intestine, in young indigenous African children. The Actin G2 gene is the main gene encoding smooth muscle actin found in enteric tissues. Recent research has identified Actin G2 alpha gene variation as an important causative biomarker in visceral myopathies and megacystis microcolon. This study of the Actin G2 gene (ACTG2) in an African population explores a possible molecular basis abnormal muscle function in a visceral myopathy.


PATIENTS AND METHODS
Following ethical permission and informed consent, DNA was extracted from whole blood samples in five patients with histologically proven African degenerative leiomyopathy. PCR amplification of ACTG2 alpha gene products by semi-automated bi-directional sequencing analysis. Results were analysed using FinchTV Sequence Alignment Software and predicting bioinformatic investigation by PolyPhen 2 software.


RESULTS
Five new patients with the ADL phenotypes were prospectively investigated for variation in the Actin G2 gamma gene (ACTG2). ACTG2 gene variation occurred in exon 5 (c.463 A>G K119R), in three (60%). In addition, intronic variation t > c-IVS3 was identified in three with the K119 mutation plus further g >  c -IVS12 and t > c + IVS16(2), suggesting a possible haplotype. Bioinformatic modelling showed that these ACTG2 gene variations are highly non-conservative altering protein expression.


CONCLUSIONS
Recurrent Actin G2 smooth muscle gene variation in African degenerative visceral leiomyopathy is associated with abnormal muscle actin development.
['Maluleke|T|T|', 'Mangray|H|H|', 'Arnold|M|M|', 'Moore|H A|HA|', 'Moore|S W|SW|']
D000199:Actins D002648:Child D004247:DNA D004252:DNA Mutational Analysis D005260:Female D014644:Genetic Variation D006627:Hirschsprung Disease D006801:Humans D015994:Incidence D007418:Intestinal Pseudo-Obstruction D008297:Male D009154:Mutation D010641:Phenotype D016133:Polymerase Chain Reaction D013019:South Africa
Visceral myopathy African degenerative leiomyopathy Children ADL