title: Mutations in MTP gene in abeta- and hypobeta-lipoproteinemia.
abstract: Familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL) are inherited disorders of apolipoprotein B (apo B)-containing lipoproteins that result from mutations in apo B and microsomal triglyceride transfer protein (MTP) genes, respectively. Here we report three patients with severe deficiency of plasma low-density lipoprotein (LDL) and apo B. Two of them (probands F.A. and P.E.) had clinical and biochemical phenotype consistent with ABL. Proband F.A. was homozygous for a minute deletion/insertion (c.1228delCCCinsT) in exon 9 of MTP gene predicted to cause a truncated MTP protein of 412 amino acids. Proband P. E. was heterozygous for a mutation in intron 9 (IVS9-1G>A), previously reported in an ABL patient. We failed to find the second pathogenic mutation in MTP gene of this patient. No mutations were found in apo B gene. The third proband (D.F.) had a less severe lipoprotein phenotype which was similar to that of heterozygous FHBL and appeared to be inherited as a co-dominant trait. However, he had no mutations in apo B gene. He was found to be a compound heterozygote for two missense mutations (D384A and G661A), involving highly conserved regions of MTP. Since this proband was also homozygous for varepsilon2 allele of apolipoprotein E (apo E), it is likely that his hypobetalipoproteinemia derives from a combined effect of a mild MTP deficiency and homozygosity for apo E2 isoform.
authors.affiliation: Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via Campi 287, I-41100 Modena, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Di Leo
authors.forename: Sandra
authors.initials: S
authors.lastname: Lancellotti
authors.forename: Junia Y
authors.initials: JY
authors.lastname: Penacchioni
authors.forename: Angelo B
authors.initials: AB
authors.lastname: Cefalù
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.forename: L
authors.initials: L
authors.lastname: Pisciotta
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
authors.forename: Carlo
authors.initials: C
authors.lastname: Gabelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
mesh_terms: D000012:Abetalipoproteinemia / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010375:Pedigree; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein