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Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients.
Hum Mutat 1995; 5(1):34-42HM

Abstract

The molecular basis of mitochondrial acetoacetyl-CoA thiolase (T2) deficiency was studied in two patients (GK11 and GK16). Fibroblasts from each patient had detectable immunoreactive T2 polypeptide (CRM). In pulse-chase experiments, fibroblasts from GK11 had two types of CRM: one (type I CRM) disappeared after a 24-hr chase and migrated more slowly than that of the normal control; the other (type II CRM) was detected with a small amount even after a 72-hr chase and had normal electrophoretic mobility. GK16's fibroblasts had a CRM (type III) which was also detectable even after a 72-hr chase and showed a slower mobility than type I CRM. By analyzing amplified cDNA and genomic fragments, we showed that both patients are genetic compounds; GK11 for the mutations N158D and T297M, and GK16 for the mutations A301P and IVS8 (+1). Expression analyses confirmed that mutant T2 subunits with N158D, T297M, and A301P correspond to type I, II, and III CRM, respectively. Among them, only the mutant T2 polypeptide with T297M appeared to have a detectable residual activity, in spite of its instability. Cotransfection of two cDNAs containing N158D and T297M suggested that heterotetramer formation reduces residual activity in GK11 cells.

Authors+Show Affiliations

Department of Pediatrics, Gifu University School of Medicine, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7728148

Citation

Wakazono, A, et al. "Molecular, Biochemical, and Clinical Characterization of Mitochondrial Acetoacetyl-coenzyme a Thiolase Deficiency in Two Further Patients." Human Mutation, vol. 5, no. 1, 1995, pp. 34-42.
Wakazono A, Fukao T, Yamaguchi S, et al. Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients. Hum Mutat. 1995;5(1):34-42.
Wakazono, A., Fukao, T., Yamaguchi, S., Hori, T., Orii, T., Lambert, M., ... Hashimoto, T. (1995). Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients. Human Mutation, 5(1), pp. 34-42.
Wakazono A, et al. Molecular, Biochemical, and Clinical Characterization of Mitochondrial Acetoacetyl-coenzyme a Thiolase Deficiency in Two Further Patients. Hum Mutat. 1995;5(1):34-42. PubMed PMID: 7728148.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients. AU - Wakazono,A, AU - Fukao,T, AU - Yamaguchi,S, AU - Hori,T, AU - Orii,T, AU - Lambert,M, AU - Mitchell,G A, AU - Lee,G W, AU - Hashimoto,T, PY - 1995/1/1/pubmed PY - 1995/1/1/medline PY - 1995/1/1/entrez SP - 34 EP - 42 JF - Human mutation JO - Hum. Mutat. VL - 5 IS - 1 N2 - The molecular basis of mitochondrial acetoacetyl-CoA thiolase (T2) deficiency was studied in two patients (GK11 and GK16). Fibroblasts from each patient had detectable immunoreactive T2 polypeptide (CRM). In pulse-chase experiments, fibroblasts from GK11 had two types of CRM: one (type I CRM) disappeared after a 24-hr chase and migrated more slowly than that of the normal control; the other (type II CRM) was detected with a small amount even after a 72-hr chase and had normal electrophoretic mobility. GK16's fibroblasts had a CRM (type III) which was also detectable even after a 72-hr chase and showed a slower mobility than type I CRM. By analyzing amplified cDNA and genomic fragments, we showed that both patients are genetic compounds; GK11 for the mutations N158D and T297M, and GK16 for the mutations A301P and IVS8 (+1). Expression analyses confirmed that mutant T2 subunits with N158D, T297M, and A301P correspond to type I, II, and III CRM, respectively. Among them, only the mutant T2 polypeptide with T297M appeared to have a detectable residual activity, in spite of its instability. Cotransfection of two cDNAs containing N158D and T297M suggested that heterotetramer formation reduces residual activity in GK11 cells. SN - 1059-7794 UR - https://www.unboundmedicine.com/medline/citation/7728148/Molecular_biochemical_and_clinical_characterization_of_mitochondrial_acetoacetyl_coenzyme_A_thiolase_deficiency_in_two_further_patients_ L2 - https://doi.org/10.1002/humu.1380050105 DB - PRIME DP - Unbound Medicine ER -