Chromosomal 17p13.3 microdeletion unmasking recessive Canavan disease mutation

doi:10.1016/j.ymgme.2011.09.031

Molecular Genetics and Metabolism

Volume 104, Issue 4, December 2011, Pages 706-707

https://doi.org/10.1016/j.ymgme.2011.09.031 Get rights and content

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Acknowledgments

We are grateful to Prof. G. Andria for critical review of the manuscript. This work was in part supported by the Italian Ministry of Health (Ricerca Corrente 2008–10) to GM.

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Cited by (3)

New T530C mutation in the aspartoacylase gene caused Canavan disease with no correlation between severity and N-acetylaspartate excretion
2013, Clinical Biochemistry
Citation Excerpt :
A further consideration concerns the striking differences between values of NAA in normal and CD-affected brain and concentration of NAA in urine of normal and CD-affected subjects. While in a CD-affected brain NAA is from quasi-normal to 50–70% higher than that found in the same area of a normal brain [14], in urine of a CD patient NAA is 250–700 times higher than the value detectable in healthy subjects [7,15]. This implies that in CD cerebral NAA accumulates up to a certain threshold beyond which it is somehow released into the bloodstream.
Canavan disease (OMIM 271900) is a severe autosomal recessive neurodegenerative disorder characterized by spongy degeneration of the brain and caused by mutations in the gene encoding for aspartoacylase (ASPA). The enzyme is responsible for the catalyses of the brain-specific compound N-acetylaspartate (NAA).
We report the case of two Egyptian sibling patients suspected of Canavan disease (CD) showing clinical deterioration, white matter degeneration, megalencephaly and severe intellectual impairment. The patients underwent magnetic resonance imaging (MRI) and biochemical analysis of NAA in biological fluid samples (serum and urine). Subsequently, in order to determine the mutation responsible for CD in these two sibs, a molecular biological examination was performed.
MRI findings and quantification of high NAA excretion (1378.5 and 680.1 μmol NAA/mmol creatinine in urine of 4 months and 4 years old patients, respectively) confirmed the diagnosis of CD and prompted a search for the responsible mutation. The molecular biological analysis revealed homozygosity for the substitution T530C (Ile177Thr) in the exon 4 of the ASPA gene in both sibs.
A total loss of enzymatic activity was also recorded.
The substitution T530C (Ile177Thr) results in a novel missense mutation causing a CD phenotype with severe clinical characteristics. This mutation was not previously described in the literature. In these two sibs, urinary concentration of NAA appears to correlate inversely to symptom severity and CD progression.
Congenital Adrenal Hyperplasia, Ovarian Failure and Ehlers-Danlos Syndrome due to a 6p Deletion
2014, Sexual Development
The relevance of assessing cerebral metabolic recovery for a safe return to play following concussion
2014, Concussions in Athletics: From Brain to Behavior

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Letter to the EditorChromosomal 17p13.3 microdeletion unmasking recessive Canavan disease mutation

Section snippets

Acknowledgments

Clin. Biochem.

Mol. Genet. Metab.

Letter to the Editor
Chromosomal 17p13.3 microdeletion unmasking recessive Canavan disease mutation