title: Abetalipoproteinemia caused by maternal isodisomy of chromosome 4q containing an intron 9 splice acceptor mutation in the microsomal triglyceride transfer protein gene.
abstract: Uniparental disomy (UPD), a rare inheritance of 2 copies of a single chromosome homolog or a region of a chromosome from one parent, can result in various autosomal recessive diseases. Abetalipoproteinemia (ABL) is a rare autosomal recessive deficiency of apoB-containing lipoproteins caused by a microsomal triglyceride transfer protein (MTP) deficiency. In this study, we describe a patient with ABL inherited as a homozygous intron 9 splice acceptor G(-1)-to-A mutation of the transfer protein gene. This mutation alters the splicing of the mRNA, resulting in a 36 amino acids, in-frame deletion of sequence encoded by exon 10. We analyzed chromosome 4, including MTP gene (4q22-24), using short tandem repeat markers. The proband has only his mother's genes in chromosome 4q spanning a 150-centimorgan region; ie, segmental maternal isodisomy 4q21-35, probably due to mitotic recombination. Nonpaternity between the proband and his father was excluded using 6 polymorphic markers from different chromosomes (paternity probability, 0.999). Maternal isodisomy (maternal UPD 4q) was the basis for homozygosity of the MTP gene mutation in this patient.
authors.affiliation: Second Department of Internal Medicine, Department of General Medicine School of Medicine, Kanazawa University, Takara-machi 13-1 Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: X P
authors.initials: XP
authors.lastname: Yang
authors.forename: A
authors.initials: A
authors.lastname: Inazu
authors.forename: K
authors.initials: K
authors.lastname: Yagi
authors.forename: K
authors.initials: K
authors.lastname: Kajinami
authors.forename: J
authors.initials: J
authors.lastname: Koizumi
authors.forename: H
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D000012:Abetalipoproteinemia / Q000235:genetics*; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005192:Family Health; D049669:History, 16th Century; D006801:Humans; D018404:Isochromosomes / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D008861:Microsomes / Q000737:chemistry; D009035:Mothers; D010375:Pedigree; D017354:Point Mutation; D012326:RNA Splicing; D020080:Tandem Repeat Sequences
chemical_list: D002352:Carrier Proteins; D008055:Lipids; C106092:microsomal triglyceride transfer protein