Laboratoire Of Genetique Moleculaire Humaine

Sfax, Tunisia

Laboratoire Of Genetique Moleculaire Humaine

Sfax, Tunisia

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Fendri-Kriaa N.,Laboratoire Of Genetique Moleculaire Humaine | Kammoun F.,Service De Neurologie Infantile | Salem I.H.,Laboratoire Of Genetique Moleculaire Humaine | Mkaouar-Rebai E.,Laboratoire Of Genetique Moleculaire Humaine | And 3 more authors.
European Journal of Neurology | Year: 2011

Background: Febrile seizures (FSs) relatively represent the most common form of childhood seizures. FSs are not thought of as a true epileptic disease but rather as a special syndrome characterized by its provoking factor (fever) and a typical range of 3months to 5years. Although specific genes affecting the majority of FS cases have not been identified yet, several genetic loci for FSs have been reported recently. The aim of this report is to search for the gene responsible for FSs in six affected Tunisian families. Methods: A microsatellite marker analysis was performed on the known FS and generalized epilepsy with febrile seizures plus (GEFS+) loci. According to the results obtained by statistical analyses for the six studied families and in agreement with the involvement of SCN1B gene in the GEFS+ syndrome in previous studies, SCN1B on GEFS+1 locus was considered as one of the potential candidate genes and was tested for mutations by direct sequencing. Results: A sequencing analysis of the SCN1B gene revealed a novel mutation (c.374G>T) that changed an arginine residue with leucine at position 125 of the protein. We consider that the variation R125L may affect the protein structure and stability by the loss of hydrogen bonding. Two identified single nucleotide polymorphisms that are located in a neighboring hypothetical polyadenylation were assumed to compose a putative disease-associated haplotype. Conclusion: Our results support that SCN1B is the gene responsible in one amongst the six FS Tunisian families studied and might contribute to the FS susceptibility for the five others. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.


Siala O.,Laboratoire Of Genetique Moleculaire Humaine | Fakhfakh F.,Laboratoire Of Genetique Moleculaire Humaine
Gene | Year: 2014

Gene expression is initiated by the binding of transcription factors to cis-regulatory modules such as enhancer elements binding to the Serine/Arginine proteins. Recently, we noticed an increased ability to identify the location as well as the motifs of enhancers using genome-wide information on spliceosomal factor occupancy, cofactor recruitment and chromatin modifications. In this study, we have undertaken a large-scale genomic analysis in an attempt to uncover if the exonic splicing enhancer motif binding to the SC35 and the SRp40 SR proteins is conserved among several groups of human genes. For the SRp40, the results showed that the ESE consensus is conserved among human genes. Concerning the SC35 SR protein, results showed an ESE motif conserved among human tissues and between different levels of muscular cell differentiation and within the same chromosome. However, this motif displays subtle discrepancies between genes localized in different chromosomes. These results emphasize the presence of different translational isoforms of the SFRS2 gene encoding for the SC35, or different post-translational protein maturations in different chromosomes, confirming that chromatin structure is another layer of gene regulation. These links between chromatin pattern and splicing give further mechanistic support to functional interconnections between splicing, transcription and chromatin structure, and raise the intriguing possibility of the existence of a memory for splicing patterns to be inherited through epigenetic modifications. © 2014 Elsevier B.V.


Siala O.,Laboratoire Of Genetique Moleculaire Humaine | Belguith N.,Laboratoire Of Genetique Medicale | Kammoun H.,Laboratoire Of Genetique Medicale | Kammoun B.,Service dophtalmologie | And 4 more authors.
Gene | Year: 2012

Peters plus syndrome is an autosomal recessive rare disorder comprising ocular anterior segment dysgenesis, short stature, hand abnormalities, distinctive facial features, and often other major/minor additional defects. Peters plus syndrome is related to mutations in the B3GALTL gene with only seven recently reported mutations, leading to the inactivation of the B1, 3-glucosyltransferase. In this study, we screened the B3GALTL gene in two unrelated patients with typical Peters plus syndrome. A novel homozygous c.597-2A > G mutation was identified in both patients. Bioinformatic analyses showed that this mutation modulates the pre mRNA secondary structure of the gene, and decreases the score value related to the formation of splicing loops. Moreover, the c.597-2A > G mutation is located in a CpG Island of the B3GALTL gene, suggesting a potential epigenetic role of this position including gene's methylation and regulation. These data confirm an important role of the B3GALTL gene test that provides diagnosis confirmation and improves genetic counseling for the families. © 2012 Elsevier B.V.


Maalej M.,Laboratoire Of Genetique Moleculaire Humaine | Mkaouar-Rebai E.,Laboratoire Of Genetique Moleculaire Humaine | Mnif M.,Service dendocrinologie | Mezghani N.,Laboratoire Of Genetique Moleculaire Humaine | And 4 more authors.
Pathologie Biologie | Year: 2014

Genes encoding the DNA helicase TWINKLE (C10orf2) or the two subunits of mtDNA polymerase γ (POLγ) (POLG1 and POLG2) have a direct effect on the mitochondrial DNA replication machinery and were reported in many mitochondrial disorders. Friedreich's ataxia (FRDA) is the common cause of ataxia often associated with the expansion of a GAA repeat in intron 1 of the frataxin gene (FXN). Mitochondrial DNA could be considered as a candidate modifier factor for FRDA disease, since mitochondrial oxidative stress is thought to be involved in the pathogenesis of this disease. We screened the FXN, POLG1 and C10orf2 genes in a Tunisian patient with clinical features of Friedreich's ataxia-like. The results showed the absence of the expansion of a GAA triplet repeat in intron 1 of the FXN gene. Besides, the sequencing of all the exons and their flanking regions of the FXN, POLG1 and C10orf2 genes revealed the presence of intronic polymorphisms. In addition, screening of the mtDNA revealed the presence of several mitochondrial known variations and the absence of mitochondrial deletions in this patient. The detected m.16187C>T and the m.16189T>C change the order of the homopolymeric tract of cytosines between 16184 and 16193 in the mitochondrial D-loop and could lead to a mitochondrial dysfunction by inhibiting replication and affecting protein involved in the replication process of the mtDNA which could be responsible for the clinical features of Friedreich ataxia observed in the studied patient. © 2013 Elsevier Masson SAS.


PubMed | Laboratoire Of Genetique Moleculaire Humaine and Service dendocrinologie
Type: Case Reports | Journal: Pathologie-biologie | Year: 2014

Genes encoding the DNA helicase TWINKLE (C10orf2) or the two subunits of mtDNA polymerase (POL) (POLG1 and POLG2) have a direct effect on the mitochondrial DNA replication machinery and were reported in many mitochondrial disorders. Friedreichs ataxia (FRDA) is the common cause of ataxia often associated with the expansion of a GAA repeat in intron 1 of the frataxin gene (FXN). Mitochondrial DNA could be considered as a candidate modier factor for FRDA disease, since mitochondrial oxidative stress is thought to be involved in the pathogenesis of this disease. We screened the FXN, POLG1 and C10orf2 genes in a Tunisian patient with clinical features of Friedreichs ataxia-like. The results showed the absence of the expansion of a GAA triplet repeat in intron 1 of the FXN gene. Besides, the sequencing of all the exons and their flanking regions of the FXN, POLG1 and C10orf2 genes revealed the presence of intronic polymorphisms. In addition, screening of the mtDNA revealed the presence of several mitochondrial known variations and the absence of mitochondrial deletions in this patient. The detected m.16187C>T and the m.16189T>C change the order of the homopolymeric tract of cytosines between 16184 and 16193 in the mitochondrial D-loop and could lead to a mitochondrial dysfunction by inhibiting replication and affecting protein involved in the replication process of the mtDNA which could be responsible for the clinical features of Friedreich ataxia observed in the studied patient.


Siala O.,Laboratoire Of Genetique Moleculaire Humaine | Belguith N.,Laboratoire Of Genetique Medicale | Fakhfakh F.,Laboratoire Of Genetique Moleculaire Humaine
Iranian Journal of Pediatrics | Year: 2013

Background: Peters Plus syndrome (MIM 261540) is a rare autosomal recessive condition characterized by ocular defects (typically Peters anomaly) and other systemic major/minor abnormalities. Mutations in the B3GALTL gene encoding the β-1,3-glucosyltransferase have been found in virtually all patients with typical Peters Plus syndrome. Case Presentation: We report here a female patient with severe manifestations of Peters Plus syndrome including facial dysmorphism and bilateral corneal opacity associated with left renal pyelo-calicial dilatation and sexual ambiguity. Total sequencing of the B3GALTL gene revealed no mutation in the patient. Conclusion: To our knowledge, sexual ambiguity has not previously been reported in Peters Plus syndrome so far, and renal malformation is also apparently rare in the syndrome. © 2013 by Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, All rights reserved.


Kallabi F.,Laboratoire Of Genetique Moleculaire Humaine | Salem I.H.,Laboratoire Of Genetique Moleculaire Humaine | Salah G.B.,Laboratoire Of Genetique Moleculaire Humaine | Turkia H.B.,Service de Pediatrie | And 4 more authors.
Neurodegenerative Diseases | Year: 2013

Background: X-linked adrenoleukodystrophy (X-ALD) is a recessive neurodegenerative disorder that affects the brain's white matter and is associated with adrenal insufficiency. It is characterized by an abnormal function of the peroxisomes, which leads to an accumulation of very long-chain fatty acids (VLCFA) in plasma and tissues, especially in the cortex of the adrenal glands and the white matter of the central nervous system, causing demyelinating disease and adrenocortical insufficiency (Addison's disease). X-ALD is caused by a mutation in the ABCD1 gene (ATP-binding cassette, subfamily D, member 1), which encodes the adrenoleukodystrophy protein involved in the transport of fatty acids into the peroxisome for degradation. Objective: We report here a disease-related variant in the ABCD1 gene in a 19-year-old Tunisian boy with childhood cerebral adrenoleukodystrophy. Methods: The diagnosis was based on clinical symptoms, high levels of VLCFA in plasma, typical MRI pattern and mo-lecular analysis. Results: Molecular analysis by direct sequencing of the ABCD1 gene showed the presence of a novel missense mutation c.284CA (p.Ala95Asp) occurring in the transmembrane domain in the proband, his mother and his sister. Conclusion: Using bioinformatic tools we suggest that this novel variant may have deleterious effects on adrenoleukodystrophy protein structure and function. Copyright © 2013 S. Karger AG, Basel.


Mkaouar-Rebai E.,Laboratoire Of Genetique Moleculaire Humaine | Ellouze E.,Service de Neurologie Infantile | Chamkha I.,Laboratoire Of Genetique Moleculaire Humaine | Kammoun F.,Service de Neurologie Infantile | And 2 more authors.
Journal of Child Neurology | Year: 2011

Cytochrome c oxidase is an essential component of the mitochondrial respiratory chain that catalyzes the reduction of molecular oxygen by reduced cytochrome c. In this study, the authors report the second mutation associated with Leigh syndrome in the blood and buccal mucosa of 2 affected members of a Tunisian family. It was a novel heteroplasmic missense mitochondrial mutation at nucleotide 9478 in the gene specifying subunit III of cytochrome c oxidase substituting the valine at position 91 to alanine in a highly conserved amino acid. It was found with a high mutant load in tissues derived from endoderm (buccal mucosa) and mesoderm (blood). However, it was nearly absent in tissue derived from ectoderm (hair follicles). It was absent in 120 healthy controls, and PolyPhen analysis showed that the hydropathy index changed from +1.276 to +0.242, and the number of structures of the 3D protein decreased from 39 to 32. © The Author(s) 2011.


Mkaouar-Rebai E.,Laboratoire Of Genetique Moleculaire Humaine | Kammoun F.,Service de Neurologie Infantile | Chamkha I.,Laboratoire Of Genetique Moleculaire Humaine | Kammoun N.,Laboratoire Of Genetique Moleculaire Humaine | And 3 more authors.
Journal of Child Neurology | Year: 2010

Mitochondrial DNA defects were known to be associated with a wide spectrum of human diseases and patients might present a wide range of clinical features in various combinations. In the current study, we described a patient with psychomotor and neurodevelopmental delay, mild hyperintensity of posterior periventicular white matter, generalized clonic seizures, leukodystrophy, and congenital deafness. He also had tetraplegia, with central blindness and swallowing difficulty. Brain magnetic resonance imaging (MRI) showed involvement of the interpeduncular nucleus and central tegmental tract, white matter abnormalities, and cerebellar atrophy. A whole mitochondrial genome screening revealed the presence of 19 reported polymorphisms and an undescribed A to G mutation at nucleotide 8411 (p.M16V) affecting a conserved region of the mitochondrial adenosine triphosphatase (ATPase) 8 protein. This de novo mutation was detected in heteroplasmic form (97%) and was absent in 120 controls. Thus, the m.8411A>G mutation could strongly be associated with the disease in the tested patient. © 2010 The Author(s).


PubMed | Laboratoire Of Genetique Moleculaire Humaine
Type: Case Reports | Journal: Gene | Year: 2012

Peters plus syndrome is an autosomal recessive rare disorder comprising ocular anterior segment dysgenesis, short stature, hand abnormalities, distinctive facial features, and often other major/minor additional defects. Peters plus syndrome is related to mutations in the B3GALTL gene with only seven recently reported mutations, leading to the inactivation of the B1, 3-glucosyltransferase. In this study, we screened the B3GALTL gene in two unrelated patients with typical Peters plus syndrome. A novel homozygous c.597-2A>G mutation was identified in both patients. Bioinformatic analyses showed that this mutation modulates the pre mRNA secondary structure of the gene, and decreases the score value related to the formation of splicing loops. Moreover, the c.597-2A>G mutation is located in a CpG Island of the B3GALTL gene, suggesting a potential epigenetic role of this position including genes methylation and regulation. These data confirm an important role of the B3GALTL gene test that provides diagnosis confirmation and improves genetic counseling for the families.

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