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

BMC Genetics

Annick Salzmann⁴  Alain Malafosse⁴  Amel Benammar Elgaaied¹  Hela Khiari Mrabet³  Chiraz Bouchlaka Souissi¹  Michel Guipponi²  Amel Mrabet³  Frédérique Bena²  Nejla Belhedi³ 

[1] Laboratory of Genetics, Immunology and Human Pathologies, University Tunis el ManarTunisia, Tunis, 2092, Tunisia;Department of Genetic Medicine and Laboratory, University Hospitals of Geneva, Geneva, Switzerland;Neurological Department, Charles Nicolle Hospital, Tunis, Tunisia;Department of Psychiatry, University of Geneva, Geneva, Switzerland

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

Others  :  1086596
DOI  :  10.1186/1471-2156-14-93

 received in 2012-11-14, accepted in 2013-09-11,  发布年份 2013

【 摘 要 】

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+.

【 授权许可】

   
2013 Belhedi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 8.

Figure 2.

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