Two patients with Canavan disease and structural modeling of a novel mutation

Canavan disease (CD) is a rare fatal childhood neurological autosomal recessive genetic disease caused by mutations in the ASPA gene, which lead to catalytic deficiency of the ASPA enzyme, which catalyzes the hydrolysis of N -acetyl-L-aspartate (NAA) into aspartate and acetate. CD occurs frequently...

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Published in:	Metabolic brain disease Vol. 32; no. 1; pp. 171 - 177
Main Authors:	Zaki, Osama K, Krishnamoorthy, Navaneethakrishnan, El Abd, Heba S, Harche, Soumaya A, Mattar, Reem A, Al disi, Rana S, Nofal, Mariam Y., El Bekay, Rajaa, Ahmed, Khalid A, George Priya Doss, C, Zayed, Hatem
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-02-2017 Springer Nature B.V
Subjects:	Biochemistry Biomedical and Life Sciences Biomedicine Brain - diagnostic imaging Canavan Disease - diagnostic imaging Canavan Disease - genetics Canavan Disease - metabolism Humans Infant Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Male Metabolic Diseases Models, Molecular Mutation Mutation, Missense Neurology Neurosciences Oncology Original Article Protein Conformation Canavan disease MRI In silico mutagenesis Molecular modeling Aspartoacylase N-acetyl-aspartate MRS
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Summary:	Canavan disease (CD) is a rare fatal childhood neurological autosomal recessive genetic disease caused by mutations in the ASPA gene, which lead to catalytic deficiency of the ASPA enzyme, which catalyzes the hydrolysis of N -acetyl-L-aspartate (NAA) into aspartate and acetate. CD occurs frequently among Ashkenazi Jewish population, however it has been reported in many other ethnic groups with significantly lower frequency. Here, we report on two Egyptian patients diagnosed with CD, the first patient harbors five missense mutations (c.427 A > G; p. I143V, c.502C > T; p. R168C, c.530 T > C; p. I177T, c.557 T > C; p. V186D c.548C > T; p. P183L) and a silent mutation (c.693 C > T; p. Y231Y). The second patient was found to be homozygous for two missense mutations (c.427 A > G; p. I143V and c.557 T > A; p. V186D). Furthermore, molecular modeling of the novel mutation p. P183L provides an instructive explanation of the mutational impact on the protein structure that can affect the function of the ASPA. Here, the clinical, radiological, and biochemical profile of the two patients are reviewed in details.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0885-7490 1573-7365
DOI:	10.1007/s11011-016-9896-9