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Establish the genomic organization of the carnitine palmitoyltransferase II gene and characterize novel disease-causing mutations in affected patients.

January 1, 1995Human Molecular Genetics

Carnitine palmitoyltransferase II deficiency: structure of the gene and characterization of two novel disease-causing mutations

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EVElisabetta VerderioNottingham Trent University PCPatrizia CavadiniIstituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna "Bruno Ubertini"LMLaura MonterminiMcGill University Health Centre

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Mutational analysis uncovers two novel destabilizing gene variants in carnitine palmitoyltransferase II deficiency, indicating impaired enzyme stability as a cause of skeletal muscle metabolic...

Key Points

Establish the genomic organization of the carnitine palmitoyltransferase II gene and characterize novel disease-causing mutations in affected patients.
Determined the genomic structure of the carnitine palmitoyltransferase II gene on chromosome 1p32, defining the 5 exons, intron-exon boundaries, and untranslated regions.
Amplified and directly sequenced exons from patients with carnitine palmitoyltransferase II deficiency across Italian, Dutch, and French ancestries.
Conducted transfection assays in COS cells and biochemical analyses in patient-derived cultured cells to evaluate catalytic activity, substrate binding, and protein stability.
Identified two novel mutations: a C665A transversion (P50H) in exon 1 affecting a conserved leucine-proline motif and a G2173A transition (D553N) in exon 5 creating a new MseI site.
Transfection experiments in COS cells demonstrated that both P50H and D553N drastically depressed carnitine palmitoyltransferase II catalytic activity, while biochemical testing showed P50H does not alter substrate binding sites.
Immunoblot analysis revealed markedly reduced steady-state levels for both mutant proteins, confirming that decreased protein stability underpins the enzymatic deficiency.

Cite This Study

Verderio et al. (1995) studied this question.

synapsesocial.com/papers/6a97f8722b5b2a1696e18052 https://doi.org/10.1093/hmg/4.1.19

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Implication

Mutational analysis uncovers two novel destabilizing gene variants in carnitine palmitoyltransferase II deficiency, indicating impaired enzyme stability as a cause of skeletal muscle metabolic...

Carnitine palmitoyltransferase II deficiency: structure of the gene and characterization of two novel disease-causing mutations

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Cite This Study

Carnitine palmitoyltransferase II deficiency: structure of the gene and characterization of two novel disease-causing mutations

Discussion

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Implication

Key Points

Cite This Study

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