31 Novel ACTG2 gene variations in familial Degenerative Leiomyopathy results in protein alteration
Twani Maluleke, Monique Zaahl, Sam Moore
University of Stellenbosch, Cape Town, South Africa


Aim: Visceral myopathies remain difficult and frustrating clinical entities, creating dilemmas for both gastroenterologist and Paediatric surgeons. A distinctive form of acquired degenerative visceral myopathy, African Degenerative leiomyopathy (ADL) is a cause of progressive intestinal pseudo-obstruction. Familial cases are uncommon but raise the question of a genetic predisposition

Recent research has shown diminished expression of enteric alpha smooth muscle actin in  megacystis microcolon  and other visceral myopathies due to haploinsufficiency of  the gene (ACTG2) that encodes actin gamma 2; a smooth muscle actin.

In this report we report the first significant ACTG2 mutation (Valine for Serine at position 160 in exon 7) in a family with AD with resulting significant changes in the mutant residue.  
Following informed consent (Ethics no. 019/2001), successful PCR DNA amplifications on blood samples were subjected to semi-automated bi-directional sequencing analysis, results being compared to the ACTG2 reference sequence. Two African sisters with a chronic history of intestinal pseudo-obstruction and a histological confirmation of Degenerative Leiomyopathy were evaluated for variation within the ACTG2 gene.  
We report the first significant ACTG2 mutation (Valine for Serine at position 160in exon 7) in a family with ADL. Bioinformatic research shows this to be a significant variation in the resulting transcription of the resulting actin amino acid which results not only in an extra hydroxyl group but also a shorter hydrophobic mutant residue and changes its interaction with ATP and Ca++ metabolism
To our knowledge this variant has not been previously reported and are probably significant providing an important link to the whole spectrum of visceral myopathies.  It should be explored further as a potential therapeutic target area