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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Carboxypeptidase A6 gene (CPA6) mutations in a recessive familial form of febrile seizures and temporal lobe epilepsy and in sporadic temporal lobe epilepsy
Human Mutation, Volume 33, No. 1, Year 2012
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Description
Febrile seizures (FS) and temporal lobe epilepsy (TLE) were found in four of the seven siblings born to healthy Moroccan consanguineous parents. We hypothesized autosomal recessive (AR) inheritance. Combined linkage analysis and autozygosity mapping of a genome-wide single nucleotide polymorphism genotyping identified a unique identical by descent (IBD) locus of 9.6 Mb on human chromosome 8q12.1-q13.2. Sequencing of the 38 genes mapped within the linked interval revealed a homozygous missense mutation c.809C>T (p.Ala270Val) in the carboxypeptidase A6 gene (CPA6). Screening all exons of CPA6 in unrelated patients with partial epilepsy (n = 195) and FS (n = 145) revealed a new heterozygous missense mutation c.799G>A (p.Gly267Arg) in three TLE patients. Structural modeling of CPA6 indicated that both mutations are located near the enzyme's active site. In contrast to wild-type CPA6, which is secreted and binds to the extracellular matrix where it is enzymatically active, Ala270Val CPA6 was secreted at about 40% of the level of the wild-type CPA6 and was fully active, while Gly267Arg CPA6 was not detected in the medium or extracellular matrix. This study suggests that CPA6 is genetically linked to an AR familial form of FS and TLE, and is associated with sporadic TLE cases. © 2011 Wiley Periodicals, Inc.
Authors & Co-Authors
Salzmann, Annick
Switzerland, Geneva
Université de Genève
Guipponi, Michel
Switzerland, Geneva
Hôpitaux Universitaires de Genève
Lyons, Peter J.
United States, New York
Albert Einstein College of Medicine of Yeshiva University
Fricker, Lloyd D.
United States, New York
Albert Einstein College of Medicine of Yeshiva University
Sapio, Matthew R.
United States, New York
Albert Einstein College of Medicine of Yeshiva University
Lambercy, Carmen
Switzerland, Geneva
Hôpitaux Universitaires de Genève
Burési, Catherine
Switzerland, Geneva
Hôpitaux Universitaires de Genève
Ouled Amar Bencheikh, Bouchra
Morocco, Agdal Rabat
Ibn Sina Hospital, Agdal Rabat
Lahjouji, Fatiha
Morocco, Agdal Rabat
Ibn Sina Hospital, Agdal Rabat
Ouazzani, Réda M.
Morocco, Agdal Rabat
Ibn Sina Hospital, Agdal Rabat
Crespel, Arielle
France, Montpellier
Centre Hospitalier Universitaire de Montpellier
Chaigne, Denys
France, Strasbourg
Clinique Sainte-odile
Malafosse, Alain
Switzerland, Geneva
Université de Genève
Switzerland, Geneva
Hôpitaux Universitaires de Genève
Statistics
Citations: 44
Authors: 13
Affiliations: 6
Identifiers
Doi:
10.1002/humu.21613
ISSN:
10597794
e-ISSN:
10981004
Research Areas
Cancer
Genetics And Genomics