Development of MLPA for human ACAT1 gene and identification of a heterozygous Alu-mediated deletion of exons 3 and 4 in a patient with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency

• Published in: Molecular genetics and metabolism 2013-09, Vol.110 (1-2), p.184-187
• Main Authors: Fukao, Toshiyuki, Aoyama, Yuka, Murase, Keiko, Hori, Tomohiro, Harijan, Rajesh K., Wierenga, Rikkert K., Boneh, Avihu, Kondo, Naomi
• Format: Article
• Language: English
• Subjects: Acetyl-CoA C-Acetyltransferase - deficiency; Acetyl-CoA C-Acetyltransferase - genetics; Acetyl-CoA C-Acetyltransferase - metabolism; Acetyl-CoA C-Acyltransferase - deficiency; Adolescent; Alu elements; Alu Elements - genetics; Amino Acid Metabolism, Inborn Errors; Base Sequence; Deletion; Enzymes; Exons - genetics; Female; Heterozygote; Homologous Recombination - genetics; Humans; Infant; Male; Mitochondria - enzymology; Mitochondria - genetics; Mitochondrial acetoacetyl-CoA thiolase; MLPA; Multiplex Polymerase Chain Reaction - methods; Recombination; Sequence Deletion - genetics
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2013.07.004

Mitochondrial acetoacetyl-CoA thiolase deficiency is an autosomal recessive disorder, characterized by intermittent ketoacidosis. We developed a multiplex ligation-dependent probe amplification method for mutation detection in the ACAT1 gene, which encodes this enzyme, and validated it using DNAs from two previously reported patients having partial deletion and duplication in this gene. Using this method, we identified a heterozygous deletion including exons 3–4 in a third patient, likely due to Alu-mediated non-equal homologous recombination between Alu sequences.