Aberrant mRNA splicing associated with coding region mutations in children with carnitine-acylcarnitine translocase deficiency

G in intron 2). Patient 2 was heterozygous for the same lariat branch point (-10T --> G intron 2) mutation, derived from the father, and a maternal frameshift mutation (362 del G in exon 3). Patient 3 was homozygous for a frameshift mutation (306 del C in exon 3). All of the three frameshift mutations give rise to the same stop codon at amino acid residue 127 which is predicted to cause premature protein truncation. In addition, cDNA transcript analysis showed that these coding sequence mutations also increase the amount of aberrant mRNA splicing and exon skipping at distances up to 7.7 kb nucleotides from mutation sites. The data suggest that the stability of mRNA transcripts is decreased or the frequency of aberrant splicing is increased in the presence of CACT coding sequence mutations. These results confirm that CACT is the genetic locus of the recessive mutations responsible for the fatal defects of fatty acid metabolism previously associated with deficiency of translocase activity in these three cases. -->

ISSN:	1096-7192
Přístupová URL adresa:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2c384adc185d8e1ee54bf9799b14490 https://pubmed.ncbi.nlm.nih.gov/11592821
Rights:	CLOSED
Přírůstkové číslo:	edsair.doi.dedup.....b2c384adc185d8e1ee54bf9799b14490
Autor:	Ferdinando Palmieri, Heidi S. Harvie, Arupa Ganguly, Charles A. Stanley, Ronald A. Chalmers, Vito Iacobazzi, Jean-Marie Saudubray, Zhili Wang, Betty Y.L. Hsu
Rok vydání:	2001
Předmět:	Male Endocrinology Diabetes and Metabolism RNA Splicing Biology medicine.disease_cause Biochemistry Frameshift mutation Exon Endocrinology Genetics medicine Humans Carnitine-acylcarnitine translocase deficiency RNA Messenger Codon Molecular Biology Cells Cultured Mutation Point mutation Intron Infant Newborn Infant medicine.disease Molecular biology Exon skipping Stop codon Carnitine Acyltransferases Child Preschool Female
Zdroj:	Molecular genetics and metabolism. 74(1-2)
ISSN:	1096-7192
Popis:	This report describes three infants with genetic defects of carnitine-acylcarnitine translocase (CACT), an inner mitochondrial membrane carrier that is essential for long-chain fatty acid oxidation. Two of the patients were of European and Chinese origin; the third was from consanguineous Turkish parents. CACT activity was totally deficient in cultured skin fibroblasts from all three patients. Patient 1 was heterozygous for a paternal frameshift mutation (120 del T in exon 1) and a maternal lariat branch point mutation (-10 T --> G in intron 2). Patient 2 was heterozygous for the same lariat branch point (-10T --> G intron 2) mutation, derived from the father, and a maternal frameshift mutation (362 del G in exon 3). Patient 3 was homozygous for a frameshift mutation (306 del C in exon 3). All of the three frameshift mutations give rise to the same stop codon at amino acid residue 127 which is predicted to cause premature protein truncation. In addition, cDNA transcript analysis showed that these coding sequence mutations also increase the amount of aberrant mRNA splicing and exon skipping at distances up to 7.7 kb nucleotides from mutation sites. The data suggest that the stability of mRNA transcripts is decreased or the frequency of aberrant splicing is increased in the presence of CACT coding sequence mutations. These results confirm that CACT is the genetic locus of the recessive mutations responsible for the fatal defects of fatty acid metabolism previously associated with deficiency of translocase activity in these three cases.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2c384adc185d8e1ee54bf9799b14490 https://pubmed.ncbi.nlm.nih.gov/11592821 Zobrazit plný text záznamu Full Text from ScienceDirect