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

作者：Belhedi Nejla^*; Bena Frederique; Mrabet Amel; Guipponi Michel; Souissi Chiraz Bouchlaka; Mrabet Hela Khiari; Elgaaied Amel Benammar; Malafosse Alain; Salzmann Annick

来源：BMC Genetics, 2013, 14(1): 93.

DOI：10.1186/1471-2156-14-93

• Febrile seizures
• GEFS
• Autosomal recessive
• Genome wide SNPs
• Linkage analysis
• Exome sequencing

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+.

• 出版日期2013-9-25