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Open Access Research article

A new locus on chromosome 22q13.31 linked to recessive genetic epilepsy with febrile seizures plus (GEFS+) in a Tunisian consanguineous family

Nejla Belhedi12*, Frédérique Bena3, Amel Mrabet2, Michel Guipponi3, Chiraz Bouchlaka Souissi1, Hela Khiari Mrabet2, Amel Benammar Elgaaied1, Alain Malafosse34 and Annick Salzmann4

Author Affiliations

1 Laboratory of Genetics, Immunology and Human Pathologies, University Tunis el ManarTunisia, Tunis, 2092, Tunisia

2 Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia

3 Department of Genetic Medicine and Laboratory, University Hospitals of Geneva, Geneva, Switzerland

4 Department of Psychiatry, University of Geneva, Geneva, Switzerland

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BMC Genetics 2013, 14:93  doi:10.1186/1471-2156-14-93

Published: 25 September 2013

Abstract

Background

Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with extremely variable expressivity. The aim of our study was to identify the responsible locus for GEFS+ syndrome in a consanguineous Tunisian family showing three affected members, by carrying out a genome-wide single nucleotide polymorphisms (SNPs) genotyping followed by a whole-exome sequencing. We hypothesized an autosomal recessive (AR) mode of inheritance.

Results

Parametric linkage analysis and haplotype reconstruction identified a new unique identical by descent (IBD) interval of 527 kb, flanking by two microsatellite markers, 18GTchr22 and 15ACchr22b, on human chromosome 22q13.31 with a maximum multipoint LOD score of 2.51. Our analysis was refined by the use of a set of microsatellite markers. We showed that one of them was homozygous for the same allele in all affected individuals and heterozygous in healthy members of this family. This microsatellite marker, we called 17ACchr22, is located in an intronic region of TBC1D22A gene, which encodes a GTPase activator activity. Whole-exome sequencing did not reveal any mutation on chromosome 22q13.31 at the genome wide level.

Conclusions

Our findings suggest that TBC1D22A is a new locus for GEFS+.

Keywords:
Febrile seizures; GEFS+; Autosomal recessive; Genome wide SNPs; Linkage analysis; Exome sequencing