Mental retardation (MR) is a group of heterogeneous clinical conditions. There are more than 900 genetic disorders associated with MR and it affects around 3% of the general population. Many MR conditions described are syndromic, fragile... more
Mental retardation (MR) is a group of heterogeneous clinical conditions. There are more than 900 genetic disorders associated with MR and it affects around 3% of the general population. Many MR conditions described are syndromic, fragile X syndrome being the most common clinical entity among them. X linked mental retardation (XLMR) is subdivided in two categories: syndromic XLMR (MRXS) when MR is associated with clinical features and non-syndromic XLMR (MRX) when MR is isolated. The aim of this systematic review of the literature was to join together the results of several studies related to X linked mental retardation and to present various genes implicated in this disease. In this review, focus has been given on genes implicated in mental retardation, the clinical data and on phenotype-genotype correlations. An exhaustive electronic and library research of the recent literature was carried out on the Web sites "Science Direct" and "Interscience Wiley". The key ...
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Research Interests: Genetics, Australia, Medicine, Israel, Genetic counseling, and 15 moreInflammatory Bowel Disease, Humans, Genetic Testing, Mutation, Europe, Jews, Cluster Analysis, Incidence, Pedigree, Phenotype, Clinical Sciences, Prevalence, Crohn Disease, Medical and Health Sciences, and Pharmacology and pharmaceutical sciences
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The prevalence of mental retardation in the general population is about 3% and chromosomal abnormalities are observed in 10 to 40% of cases and make up the first genetic cause of this pathology. But for 60% of patients there is no... more
The prevalence of mental retardation in the general population is about 3% and chromosomal abnormalities are observed in 10 to 40% of cases and make up the first genetic cause of this pathology.
But for 60% of patients there is no etiology because there is no characteristic phenotype.
With molecular cytogenetics technics (FISH) 6 to 8% of idiopathic cases are related to subtelomeric rearrangements and many studies involves chromosomes telomeres in about 10% of mental retardation.
The authors report an application of subtelomeric FISH in Tunisian patients and discuss the interest of this technic in exploring mental retardation in Tunisia.
But for 60% of patients there is no etiology because there is no characteristic phenotype.
With molecular cytogenetics technics (FISH) 6 to 8% of idiopathic cases are related to subtelomeric rearrangements and many studies involves chromosomes telomeres in about 10% of mental retardation.
The authors report an application of subtelomeric FISH in Tunisian patients and discuss the interest of this technic in exploring mental retardation in Tunisia.
ABSTRACT Treacher Collins syndrome was first mentioned by Thompson in 1847, and described by Treacher Collins in 1900, then it was called mandibulo-facial dysostosis and well defined by Franceschetti in 1949. It is a very rare affection... more
ABSTRACT Treacher Collins syndrome was first mentioned by Thompson in 1847, and described by Treacher Collins in 1900, then it was called mandibulo-facial dysostosis and well defined by Franceschetti in 1949. It is a very rare affection occurring lin 50.000 live births, which includes facial and auricular anomalies leading to functional, morphological and psychological difficulties due to related handicaps. Treacher Collins syndrome is inherited as autosomal dominant pattern with a variable expressivity and incomplete penetrance of "TCOF1" gene localized at 5q31.3q32. Today the gene is well identified and several mutations have been reported. In this paper we report the case of 4 Tunisian unrelated girls with Treacher Collins syndrome. One of them was born from an affected father. Clinical diagnostic was performed between age 12 days and 2 years demonstrating the large dysmorphic expression. Main clinical features were present in all reported cases. Family at risk might have genetic counselling and probably prenatal diagnostic in some situations. Out of our observations, we gave genetic counselling and proposed ultrasound prenatal diagnosis for two families without molecular study.
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Nowadays, the genetic basis of mental retardation is a huge field of investigations. Genetic abnormalities frequently give rise to a mental retardation phenotype and are observed in 10 to 40% of known etiologies. New syndromes have... more
Nowadays, the genetic basis of mental retardation is a huge field of investigations. Genetic abnormalities frequently give rise to a mental retardation phenotype and are observed in 10 to 40% of known etiologies. New syndromes have identified (chromosome 1p, 22q, 3q29 and 9q34) but for 60% of patients there is no etiology because there is no characteristic phenotype. Many studies involve subtelomeric duplications and deletions in idiopathic mental retardation. The autours describe and discuss the interest and the limits of telomeric FISH [Chromoprobe Multiprobe T System] in exploring mental retardation.
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In this study we examined the deletion of SMN and NAIP genes in 60 Tunisian families. There were 35 patients with type I SMA. 18 with type II SMA. 6 with type III SMA and I with type IV SMA. The age of onset was before 6 months for type... more
In this study we examined the deletion of SMN and NAIP genes in 60 Tunisian families. There were 35 patients with type I SMA. 18 with type II SMA. 6 with type III SMA and I with type IV SMA. The age of onset was before 6 months for type I, between 6 months and 2 years for type II, between 2 years and 17 years for type III and 30 years for type IV. Exon 7 of SMNI gene was homozygously deleted in 95% (57/60) of SMA patients. There was a higher frequency of homozygous absence of SMN1 in type I and type II (100% and 94% respectively) than in type III (66,7%). SMN1 exon 8 was undetectable in 88% (53/60) of patients. The case type II patient with homozygous deletion of SMNI exon 7 and not exon 8 was tested for the presence of a hybrid SMN gene. This patient showed in the second PCR a SMN1 exon 8 product by restriction site assay indicating that a gene conversion event had occurred. All parents' individuals retained one copy of their SMN1 gene. Exon 5 of NAIP gene was homozygously dele...
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The Androgen insensitivity syndrome (AIS) in its complete form (CAIS) is a disorder in abnormal male development characterized by a complete female phenotype in a 46,XY individual. The most frequent cause of this disorder is a hemizygous... more
The Androgen insensitivity syndrome (AIS) in its complete form (CAIS) is a disorder in abnormal male development characterized by a complete female phenotype in a 46,XY individual. The most frequent cause of this disorder is a hemizygous mutation in androgen receptor (AR) gene located in X chromosome. The first aim of this study was to confirm the clinical diagnosis in a series of Tunisian patients with a typical phenotype of CAIS by molecular genetic analysis. The second aim was to determine the AR mutational profile in the local population. The entire coding region and the exon-intron junctions of the AR gene were sequenced in a series of ten patients. AR defects were found in nine patients. Despite the small number of cases, two of the nine identified mutations were novel. The first novel mutation was an 8-bp deletion in exon 1 (c.862_869del) resulting in a frameshift (p.A288Qfs*14). The second was a splice site mutation c.1885+1G>T (IVS3+1G>T). In this study, genetic testing has confirmed the diagnosis of most CAIS patients and has revealed two novel mechanisms responsible for the pathogenesis of AIS, as well as seven other reported mutations.
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Research Interests: Medical Genetics, Biology, Medicine, Biological Sciences, Humans, and 12 moreAlstrom syndrome, Bardet-Biedl syndrome, Genetic Testing, Genetic Association Studies, Proteins, Human Genome, Reproducibility of Results, Cell Cycle Proteins, Cohort Studies, DNA mutational analysis, genetic heterogeneity, and Medical and Health Sciences
Earlier we had reported a large prevalence of the Q318X mutation in the CYP21A2 gene with 35.3% in Tunisian patients with a classical form of 21-hydroxylase deficiency, in contrast with 0.5% to 13.8% as described in other populations.... more
Earlier we had reported a large prevalence of the Q318X mutation in the CYP21A2 gene with 35.3% in Tunisian patients with a classical form of 21-hydroxylase deficiency, in contrast with 0.5% to 13.8% as described in other populations. Here we present the analysis of the ...
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The contribution of BRCA1/BRCA2 mutations to hereditary breast cancer in the Tunisian population has not been accurately estimated. The purpose of our study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1/2... more
The contribution of BRCA1/BRCA2 mutations to hereditary breast cancer in the Tunisian population has not been accurately estimated. The purpose of our study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1/2 genes in early onset and familial breast/ovarian cancer among Tunisian women. To identify predictive factors for BRCA1/2 mutations, we screened the entire coding sequences and intron/exon boundaries of BRCA1/BRCA2 genes in 48 patients by direct sequencing. Twelve pathogenic mutations were detected (25%); three in BRCA1 (c.211dupA in four families, c.5266dupC in three families and c.1504_1508delTTAAA in one family) and two novel mutations in BRCA2 (c.1313dupT in two families and c.7654dupT in two families). We also identified 23 different polymorphisms and unclassified variants. These results indicate that our population has a spectrum of recurrent BRCA mutations.
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Turner's syndrome (TS) affects about 1/2500 female infants born alive. The syndrome results from total or partial absence of one of the two X chromosomes normally present in females. We report the results of a retrospective analysis... more
Turner's syndrome (TS) affects about 1/2500 female infants born alive. The syndrome results from total or partial absence of one of the two X chromosomes normally present in females. We report the results of a retrospective analysis of 89 cases of TS observed during a six-year period (2000–2005). The patients’ age ranged from two days to 51 years at the time of this analysis. Most patients were adults (48%). The aim of this study is to ascertain the principal clinical features leading to a request for a karyotype, searching for a possible relationship between chromosomal anomalies and clinical expression of TS. Pediatric patients were referred for statural retardation or dysmorphic features, while reproduction anomalies were the main indication for karyotyping in patients aged over 20 years. Mosaicism was prevalent (47%), whereas the homogeneous karyotype 45,X was found in only 32% of the patients; structural anomalies were found in 21%. Regarding the advanced age of our patien...
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Background and aims: Crohn's disease is a multifactorial disorder with a pivotal role of the genetic component. HSP70-2 gene, located in IBD3 region, has a PstI polymorphic site associated recently with Crohn's disease... more
Background and aims: Crohn's disease is a multifactorial disorder with a pivotal role of the genetic component. HSP70-2 gene, located in IBD3 region, has a PstI polymorphic site associated recently with Crohn's disease especially with a perforating form. In this study, we sought to ...
Research Interests: Genetics, Polymorphism, Adolescent, Multivariate Analysis, Humans, and 15 moreFemale, Male, Polymerase Chain Reaction, Phenotype, Clinical Sciences, European, Middle Aged, Genotype, Adult, Asian Continental Ancestry Group, Heat Shock Protein, Crohn Disease, Case Control Studies, Severity of Illness Index, and Gene frequency
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The prevalence of mental retardation in the general population is about 3% and chromosomal abnormalities are observed in 10 to 40% of cases and make up the first genetic cause of this pathology. But for 60% of patients there is no... more
The prevalence of mental retardation in the general population is about 3% and chromosomal abnormalities are observed in 10 to 40% of cases and make up the first genetic cause of this pathology. But for 60% of patients there is no etiology because there is no characteristic phenotype.
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Cytogenetic prenatal diagnosis (PND) is under national health program in most developed countries, while it concerns a small part of population at risk in developing countries. Finance is common reason of absence of PND development, but... more
Cytogenetic prenatal diagnosis (PND) is under national health program in most developed countries, while it concerns a small part of population at risk in developing countries. Finance is common reason of absence of PND development, but socio-cultural believes play an important role in Arab Muslim countries. In this paper we report results of 3110 fetal karyotypes carried out in a Tunisian population, by cultured amniocytes analysis. It is the largest report in a Muslim Arab country in our Knowledge. Abnormal karyotypes rate was 4.18% classified in two groups: bad prognosis (3.05%) and good prognosis (1.13%). Common amniocentesis indication was maternal age. The highest predictive value was observed in balanced karyotype and fetal ultrasound findings indications. Maternal serum markers were not commonly used for trisomy 21 screening. Pregnancy termination that is permitted by legal and religious authorities was accepted by 94,74% parents. Information about PND outcomes was given by genetic counselling prior to fetal sampling, pregnancy interruption was discussed with parents at cytogenetic result announcement. The authors conclude that in order to prevent mental and physical handicap related to cytogenetic disorders we have to promote PND by education for population, genetic counselling and fetal ultrasound screening; all three methods available in Tunisia.
Research Interests: Population Genetics, Health Education, Ultrasound, Islam, Genetic counseling, and 19 morePregnancy, Humans, Developing Country, Genetic Testing, Tunisia, genetic Counselling, Female, Karyotyping, High risk pregnancy, Amniocentesis, Arabs, Adult, Maternal Age, Prognosis, Prenatal Diagnosis, Chromosome Disorders, Chromosomal abnormalities, Predictive value of tests, and Chromosome Banding
... Azzabi a , A. Barhoumi a , Corresponding Author Contact Information , E-mail The Corresponding Author , S. Omar b , L. Ben Hassine a , E ... L'homocystéine est un acide aminé soufré, découvert en 1933 par Du Vigneaud, qui... more
... Azzabi a , A. Barhoumi a , Corresponding Author Contact Information , E-mail The Corresponding Author , S. Omar b , L. Ben Hassine a , E ... L'homocystéine est un acide aminé soufré, découvert en 1933 par Du Vigneaud, qui constitue un intermédiaire important dans la fonction ...
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Investigation of a critical region for an X-linked mental retardation (XLMR) locus led us to identify a novel Aristaless related homeobox gene (ARX ). Inherited and de novo ARX mutations, including missense mutations and in frame... more
Investigation of a critical region for an X-linked mental retardation (XLMR) locus led us to identify a novel Aristaless related homeobox gene (ARX ). Inherited and de novo ARX mutations, including missense mutations and in frame duplications/insertions leading to expansions of polyalanine tracts in ARX, were found in nine familial and one sporadic case of MR. In contrast to other genes involved in XLMR, ARX expression is specific to the telencephalon and ventral thalamus. Notably there is an absence of expression in the cerebellum throughout development and also in adult. The absence of detectable brain malformations in patients suggests that ARX may have an essential role, in mature neurons, required for the development of cognitive abilities.
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In patients with androgen insensitivity syndrome (AIS), RFLP study of the androgen receptor gene made it possible to analyze whether deletions or mutations could be responsible for abnormalities in androgen responsiveness. We studied... more
In patients with androgen insensitivity syndrome (AIS), RFLP study of the androgen receptor gene made it possible to analyze whether deletions or mutations could be responsible for abnormalities in androgen responsiveness. We studied RFLPs of DNA from 25 46,XY patients with partial AIS (PAIS), defined as a concentration of androgen receptor in genital-skin fibroblasts less than 340 fmol/mg DNA, and DNA from 27 46,XY patients with complete AIS (CAIS) with no detectable androgen receptor site. DNA samples were digested with BamHI, EcoRI, HindIII and TaqI restriction enzymes and hybridized with three cDNA probes covering the three domains of the androgen receptor. When we had the maternal and an unaffected brother's DNA, we analyzed the two androgen receptor gene polymorphisms described, the HindIII and the exon 1 CAG repeat polymorphisms, in order to distinguish the two maternal X chromosomes, and to detect carriers of AIS. We did not find any large deletion among the 52 patients. We observed a heterozygous mother in 3 of 14 families studied with the HindIII polymorphism, and in 12 of 25 families using the exon 1 CAG repeat polymorphism. This study suggests that in AIS, abnormalities in androgen receptor response could be related to point mutations or microdeletions rather than to gross structural alterations of the androgen receptor gene. Furthermore, unless the point mutation has been described, exon 1 and HindIII polymorphism studies would enable the identification of carriers in 50% of families, and the prenatal diagnosis of AIS.
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ABSTRACT We describe two sisters who had a unique association of facial, ocular & skeletal defects and abdominal muscle hypoplasia. The two affected sisters are the fourth & the fifth sibs, born to healthy first cousin... more
ABSTRACT We describe two sisters who had a unique association of facial, ocular & skeletal defects and abdominal muscle hypoplasia. The two affected sisters are the fourth & the fifth sibs, born to healthy first cousin parents originating from Tunisia, indicating autosomal recessive inheritance. The family history is unremarkable. Many of these features overlap those previously found in other malformation syndromes. However, the constellation of defects observed in these patients appears to represent a OSA syndrome previously reported in 1996 by Mingarelli et al. In the best of our knowledge, it's the second report of this syndrome.
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Fragile X syndrome, the most prevalent inherited cause of mental retardation, is related to hyperexpansion of a polymorphic CGG repeat of the FMR1 gene. Expansion of 55-200 repeats are called premutations and characterize carriers who... more
Fragile X syndrome, the most prevalent inherited cause of mental retardation, is related to hyperexpansion of a polymorphic CGG repeat of the FMR1 gene. Expansion of 55-200 repeats are called premutations and characterize carriers who usually have no mental impairment. The disease causing full mutations exceed 200 CGG repeats, are hypermethylated and lead to transcriptional silencing of the gene and absence of the Fragile X mental retardation protein (FMRP). Diagnostic approaches involve molecular and immunocytochemical techniques. Southern blot, which allows mutations to be detected and methylation status to be determined in a single test, remains the procedure of choice for most laboratories. Modifications of PCR methods, including methylation specific PCR, are also proposed but their implementation is still in question because of inherent difficulties to amplify CGG repeats, distinguish between mosaic patterns and interpret results in female individuals. The FMRP antibody test is also suitable for large population screening and elucidation of Fragile X syndrome cases with no CGG expansion, but it is not widely applied. In search for novel diagnostic approaches, use of PCR as a first prescreening test followed by Southern blot is considered the most reliable procedure.
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Research Interests: Genetics, Adolescent, Humans, Child, Mutation, and 8 moreTunisia, Female, Clinical Genetics, Male, Clinical Sciences, Middle Aged, Adult, and Syndrome
Cleft palate with ankyloglossia (CPX; OMIM 303400) is inherited as a Mendelian semidominant X-Linked disorder. Linkage studies resulted in mapping CPX to Xq13-q 21-31 region. TBX22 was identified as causing CPX. We report a new mutation... more
Cleft palate with ankyloglossia (CPX; OMIM 303400) is inherited as a Mendelian semidominant X-Linked disorder. Linkage studies resulted in mapping CPX to Xq13-q 21-31 region. TBX22 was identified as causing CPX. We report a new mutation in a Tunisian family and the first Arab family with X-Linked cleft palate and ankyloglossia. The family includes 6 affected members, 4 males and 2 females. Linkage study was performed using 9 microsatellite markers surrounding the CPX locus with a maximum lod score 1.81 at theta=0 with several markers. Sequence analysis of TBX22 gene revealed a novel change c.358C>T in exon 3 (R120W) located in the T-BOX domain; this change was present in all affected members and none of the 100 controls. A second modification in exon 4 (c.559G>A) predicted to result in a nonconservative substitution (E187 K) was present in the affected members but also in 2 controls, suggesting a polymorphism which functional role cannot be excluded without further study.