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.
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.
Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu 501-1194, Japan. toshi-gif@umin.net
Toshiyuki
T
Fukao
Yuka
Y
Aoyama
Keiko
K
Murase
Tomohiro
T
Hori
Rajesh K
RK
Harijan
Rikkert K
RK
Wierenga
Avihu
A
Boneh
Naomi
N
Kondo
D000101:Acetyl-CoA C-Acetyltransferase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency; D000293:Adolescent; D020087:Alu Elements / Q000235:genetics*; D000592:Amino Acid Metabolism, Inborn Errors; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D005260:Female; D006579:Heterozygote; D059765:Homologous Recombination / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D017384:Sequence Deletion / Q000235:genetics
D000102:Acetyl-CoA C-Acyltransferase; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase
Alu elements; Deletion; MLPA; Mitochondrial acetoacetyl-CoA thiolase; Recombination; T2