Mouse Anti-Mycetozoa Actin Hybridoma [BDU JW]

IntroductionVisceral 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 methodsFollowing 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.ResultsFive 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.ConclusionsRecurrent Actin G2 smooth muscle gene variation in African degenerative visceral leiomyopathy is associated with abnormal muscle actin development.

The aim of this study was to identify the underlying molecular mechanism for the development of megacystis microcolon intestinal hypoperistalsis syndrome in 4 Chinese patients. We found a c.770G>A (p.R257H) mutation in 3 patients, and a c.769C>T (p.R257C) mutation in the fourth patient by using whole-exome sequencing and targeted Sanger sequencing. The immunohistochemical investigation and transmission electron microscopy revealed an apparent defect of the intestinal smooth muscle, and hypoganglionosis. Our report suggested that R257 variant in the ACTG2 appear to be more frequent in populations of Asian ancestry; mutation of this locus could cause alterations of the intestinal and bladder smooth muscle filaments.