A new locus on chromosome 22q13.31 linked to recessive genetic epilepsy with febrile seizures plus (GEFS+) in a Tunisian consanguineous family.
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+.
Laboratory of Genetics, Immunology and Human Pathologies, University Tunis el ManarTunisia, Tunis, 2092, Tunisia. belhedinejla@yahoo.fr.
Nejla
N
Belhedi
Frédérique
F
Bena
Amel
A
Mrabet
Michel
M
Guipponi
Chiraz Bouchlaka
CB
Souissi
Hela Khiari
HK
Mrabet
Amel Benammar
AB
Elgaaied
Alain
A
Malafosse
Annick
A
Salzmann
D020413:3' Untranslated Regions; D000293:Adolescent; D044383:Black People / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003241:Consanguinity; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D004829:Epilepsy, Generalized / Q000235:genetics*; D005091:Exons; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics; D008040:Genetic Linkage; D056426:Genetic Loci; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D003294:Seizures, Febrile / Q000235:genetics*; D014416:Tunisia
D020413:3' Untranslated Regions; D020690:GTPase-Activating Proteins; C582817:TBC122A protein, human