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Bardet-Biedl syndrome ( BBS, OMIM 209900) is a rare genetic disorder characterized by obesity, retinitis pigmentosa, post axial polydactyly, cognitive impairment, renal anomalies and hypogonadism. The aim of this study is to provide a comprehensive clinical and molecular analysis of a cohort of 11 Tunisian BBS consanguineous families in order to give insight into clinical and genetic spectrum and the genotype-phenotype correlations. Molecular analysis using combined sequence capture and high-throughput sequencing of 30 ciliopathies genes revealed 11 mutations in 11 studied families. Five mutations were novel and six were previously described. Novel mutations included c. 1110G>A and c. 39delA (p.G13fs*41) in BBS1, c.115+ 5G>A in BBS2, c.1272+ 1G>A in BBS6, c.1181_1182insGCATTTATACC in BBS10 (p. S396Lfs*6). Described mutations included c. 436C>T (p. R146*) and c.1473+ 4A>G in BBS1, c. 565C> (p. R189*) in BBS2, deletion of exons 4-6 in BBS4, c. 149T>G (p. L50R) in BBS5, and c.459+ 1G>A in BBS8; most frequent mutations were described in BBS1 (4/11, 37%) and BBS2 (2/11, 18%) genes. No phenotype-genotype correlation was evidenced. This data expands the mutations profile of BBS genes in Tunisia and suggests a divergence of the genetic spectrum comparing Tunisian and other populations. [ABSTRACT FROM AUTHOR]

Gaucher’s disease is one of the rare lysosomial disease that could receive substitutive enzymatic treatment which may improve considerably the prognosis of certain forms. The purpose of this work is to study the epidemiology of the disease in Tunisia, to highlight the diagnostic and therapeutic difficulties and also to precise our subsequent needs for substitutive medication.Patients and methods.– We have conducted a retrospective survey of the hospital wards that were susceptible to take care of patients having Gaucher’s disease. These wards are the paediatric, neonatology, internal medicine, haematology, neurology and cardiology wards.Results.– In this study we have observed 27 cases of Gaucher’s disease over a period of 18 years (1983–2001). The age at onset ranges from birth to 73 years of age, with an average age of 14.5 years. According to the age at onset and the clinical presentation, we classify our patients into: 20 cases of type 1 (74%), three cases of type 2 (12%), and three cases of type 3 (12%), and one case of unspecified type.

The article discusses the study on the mutations in the forkhead transcription factor gene FOXL2 in patients with blepharophimosis-ptosis-epicanthus inversus syndome (BPES) in Tunisia. It cites that the study distinguished two clinical types, the BPES type I associated with premature ovarian failure (POF), and BPES type II without POF. Overviews on the materials and methods used in the study are presented, along with the data gathered on the FOXL2 mutations screening.

Abstract: Aim: To determine frequency of Y microdeletions in azoospermic and oligospermic Tunisian infertile males. Methods: A Sample of 146 Tunisian infertile males with a low sperm count (<5×106 sperms per mililiter) and normal karyotype was screened for Y chromosome microdeletions. 76 men were azoospermic and 70 men were oligospermic. Genomic DNA was isolated from blood and multiplex PCR was carried out with a set of 20 AZFa, AZFb and AZFc STS markers to detect the microdeletions as recommended by the European Academy of Andrology. Results: In 10/146 (6.85%) subjects AZF deletions were observed. Of these ten males with microdeletions, 9/10 subjects were azoospermic (90%), 1/10 was oligospermic (10%). Frequency of microdeletions in azoospermic men was 9/76 (11.84%). None of the patients showed isolated microdeletion in the AZFa region, but one azoospermic man had deletion in the AZFb region. Eight azoospermic patients and one oligospremic man have AZFc microdeletions. AZFc and AZFb were deleted in three azoospermic patients. AZFc, AZFb and AZFa were deleted in three azoospermic patients We estimate the sensitivity of the test comprising six STS in our sample to be 90%. Conclusion: The incidence of Yq microdeletions in the study population of infertile Tunisian men falls within the range published in other countries. We suggest to analyze 9STS in the first step to detect efficiently Y microdeletions in our population. [Copyright &y& Elsevier]

Abstract: Mucopolysaccharidosis type I (MPS I) is a lysosomal disease due to mutations in the gene encoding α-l-iduronidase (IDUA) leading to variable clinical phenotypes with progressive severe organomegaly, bone and neurological involvement in the most severe forms. The aim of our study was to propose in Tunisia a strategy of molecular and prenatal diagnosis of the MPS I. Population and methods: Our study was carried out on 8 MPS I patients recruited from different Tunisian regions and issued from 5 unrelated families. All the patients were offspring of consanguineous marriages. Results: The clinical and biological study led to diagnose 5 Hurler patients and 3 Hurler–Scheie patients. Three IDUA mutations were identified by molecular analysis within 6 different families: a novel mutation p.F602X and 2 already described mutations p.P533R and p.R628X. Discussion: MPS I is a heterogeneous disease characterized by variability of the phenotypes. The missense mutation p.P533R associated with the intermediate phenotype was the most frequent in the Tunisian but also in the Moroccan population. In Tunisia, the incidence of p.P533R mutation seems to be associated with the high frequency of consanguineous marriages. Conclusion: The identification of known MPS I mutations (p.P533R and p.R628X) and of the novel mutation p.F602X permits reliable genetic counselling of at-risk relatives and molecular prenatal diagnosis. [Copyright &y& Elsevier]

The levels of metallic trace elements were determined in fishery products sampled from Tunisian fishing ports. Mean concentrations were 0.20 ± 0.01, 0.05 ± 0.01, and 0.10 ± 0.01 mg/kg in fish flesh for Hg, Cd, and Pb, respectively. The mean concentrations of these elements were below regulatory thresholds; however, we also detected some specimens with higher levels. The mercury level showed a significant difference between fish categories, region, and year of sampling (p < 0.05). Samples from the center sites had the highest levels of Pb (0.17 ± 0.03 mg/kg; range 0.10; 0.22 mg/kg). Temporal analysis of Pb showed a significant difference between sampling year (p < 0.05). In addition, distribution among fish categories was statistically significant (p = 0.046). The rates of samples exceeding limits of Hg, Cd, and Pb were 5.3, 2.6, and 0.4%, respectively. Through the above results, the maximum weekly and monthly intakes for fish flesh consumption could not exceed the set limits. These data were important to inform consumers about fish content and the risk generated by some of these species.

Background: Mutations in SQSTM1 gene have been recently identified as a rare cause of progressive childhood neurodegenerative disorder. So far, only 25 patients from 10 unrelated families were reported., Methods and Results: We report on the first Tunisian case of an 11-year-old girl with cerebellar ataxia, chorea and ophthalmoparesis. Brain MRI was normal. Whole-exome sequencing revealed a homozygous mutation c.823&#95;824del(p.Ser275Phefs*17) in SQSTM1 gene (GenBank: NM&#95;003900.4)., Conclusion: By pooling our data to the data of literature, we delineated the phenotypic spectrum and stressed on genetic heterogeneity of this rare neurodegenerative disease., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Marshall syndrome is a rare autosomal dominant skeletal dysplasia. It associates a particular facial dysmorphism with midface hypoplasia, ocular abnormalities and sensorineural hearing loss. It is caused by heterozygous mutations in COL11A1 gene coding the 1 chain of collagen XI. Stickler syndrome is the principal differential diagnosis of Marshall syndrome., Aim: Clinical and radiological study of Marshall syndrome in a Tunisian family with a linkage study of the COL11A1 gene to this disease., Methods: We report the clinical and the radiological findings of a Tunisian family including 8 members affected by Marshall syndrome. The linkage of the COL11A1 gene to this disease was tested using the polymorphic microsatellite markers of DNA., Results: A variability of the clinical expression of Marshall syndrome was reported. Specific Marshall phenotype and an overlapping phenotype between the Marshall and Stickler syndromes were observed among the affected members of this family. The ocular manifestations were also heterogeneous. Marshall syndrome's specific radiological signs were found. The linkage study supports the linkage of the abnormal phenotype to the COL11A1 gene., Conclusion: There is a variability of the clinical expression among the affected members of the study's family. We will continue searching the causative mutation to establish a clear genotype- phenotype correlation.

Intellectual Deficiency (ID) is a common neuropsychiatric disorder whose etiopathogenesis still insufficiently understood. In the last decade, several surveys, assessing epidemiologic, clinical and etiologic parameters of ID, have been performed but none of them is realized in a Tunisian population. In this retrospective survey, we propose to study these parameters, in a Tunisian cohort of 458 patients with constitutional ID, and to assess our diagnostic strategy. Data analyses, by the SPSS program, reveal a male predominance, a high level of consanguinity, an advanced mean age of patients, a rare frequentation of specialized institutions by the severely affected patients, and a high frequency of familial forms with predominance of the recessive autosomal ones. The study of clinical parameters and investigations' results shows that 72.1% of our patients present a syndromic ID. For these patients, chromosomal anomalies are rarely described, EEG anomalies were usually non-specific in patients without clinical evidence of epilepsy, and brain anomalies are common in patients with severe ID, neurological symptoms or history of seizures. Aetiology is identified in 13.1% of them whereas it is still unknown in 100% of patients with non-specific ID. This study allows us to better characterize, epidemiologically and clinically, the first large Tunisian cohort of patients with ID and to assess our diagnostic strategy in order to propose a revised one that will improve the diagnostic lead, the care chain and the preventive resources of ID., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Unlabelled: Acquiring rubella during the first 20 weeks of pregnancy can lead to teratogenic effects., Aim: The aim of the study was to investigate the impact of rubella vaccination strategy two years after its introduction in Tunisia in 2005., Methods: This study was conducted over two periods, 2000 and 2007-2008. A total of 15,776 childbearing women were enrolled in the sample. Serological studies were performed by using the ELISA method., Results: Overall, rubella infection seroprevalence did not increase between 2000 and 2007-2008. Nevertheless, a significant increase in seroprevalence, from 78.2% in 2000 to 92% in 2007-2008 (P=0.006), was especially noted in the age group under 20 years. Seroprevalence did also statistically increase with parity in 2007-2008 from 77.4% in women without any parity to 89.8% in women with over three parities (P=0.01)., Conclusions: Results improvements seem most likely due to mass vaccination campaign for girls aged from 13 to 18 years in 2005, and also routinely post-partum vaccination of seronegative pregnant women or women ignoring their rubella status. In the coming years, systematic selective immunization of 12-year-old schoolgirls who are not yet entering their prime childbearing years will achieve female population sufficient immunity., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Steroid 11β-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, resulting in virilization, glucocorticoid deficiency and hypertension. The 11β-hydroxylase enzyme is encoded by the CYP11B1 gene and mutations in this gene are responsible for this disease. The aim of this study was to characterize mutations in the CYP11B1 gene and to determine their frequencies in a cohort of Tunisian patients. The molecular genetic analysis was performed by direct nucleotide sequencing of the CYP11B1 gene in 15 unrelated Tunisian patients suffering from classical 11β-hydroxylase deficiency. Only two mutations were detected in homozygous state in the CYP11B1 gene of all patients, the p.Q356X in exon 6 (26.6%) and the novel p.G379V in exon 7 with large prevalence (73.3%). This is the first report of screening for mutations of CYP11B1 gene in the Tunisian population and even in the Arab population., (© 2010 John Wiley & Sons A/S.)

Purpose: The PITX3 (pituitary homeobox 3) gene encodes for a homeobox bicoid-like transcription factor. When one allele is mutated, it leads to dominant cataract and anterior segment mesenchymal dysgenesis in humans. When both copies are mutated, homozygous mutation contributes to microphtalmia with brain malformations. In the current study, a family with autosomal recessive congenital cataract (ARCC) associated with mental retardation (MR) was examined to identify PITX3 mutations., Methods: Sequencing of the PITX3 gene was performed on two affected and three unaffected members of the studied Tunisian family. The results were analyzed with Sequencing Analysis 5.2 and SeqScape., Results: No mutation in the four exons of PITX3 was revealed. Two substitution polymorphisms, c.439C>T and c.930C>A, were detected in exons 3 and 4, respectively. These alterations did not segregate with the disease., Conclusions: Although PITX3 was shown to be essential to normal embryonic eye and brain development in vertebrates, we report the absence of PITX3 mutations in a family presenting congenital cataract and mental retardation.

Background: The mucopolysaccharidoses (MPS) are a devastating heterogenous group of lysosomal storage disorders., Aim: To evaluate the epidemiological profile of MPS in Tunisia., Methods: we conducted a retrospective epidemiological survey covering the period 1970-2005. Multiple sources were used to identify affected patients., Results: Ninety six confirmed MPS cases were collected from 132 suspected cases found in the surveyed data. Of the ninety six confirmed cases, 20% were from multiplex families. Consanguinity was found in 83% of the families. The crude rate for all types of mucopolysaccharidoses was 2.3 cases in 100,000 live births. The prevalence of MPS type I, III and IV, those most frequently occurring in the collected data, were estimated at 0.63, 0.7 and 0.45 per 100,000 live births, respectively. The cumulative incidence of MPS type VI (0.3 per 105 live births) was higher than reported in European countries; but, it is likely that..., Conclusion: The reported frequency of all types of MPS in Tunisia is underestimated.

The aim of the study was to assess hepatitis A virus (HAV) seroprevalence in blood donors from South Tunisia in two periods 2000 and 2007. Serum samples collected from 376 blood donors in each period aged 18 to 30 years from different regions of South Tunisia were analysed for anti-HAV IgG. The global seroprevalence of HAV infection was 85.9% in 2007 as compared with 94.9% in 2000. The seroprevalence in the 18-20 years age group was 91.9% in 2000 vs 80.6% in 2007, and increased to 99% in 2000 and 92% in 2007 in the subjects over 26. Taking account of geographic area, the HAV seroprevalence in Sfax city decreased from 88.9% in 2000 to 62.7% in 2007 (p < 0.001), but it is still approximatively the same in rural areas (98.4% and 96%) and in the governorates of South Tunisia (97.6% and 99.2%). In conclusion, the number of adults in the city of Sfax which are not immunized against HAV is increasing. Thus, adolescents and young adults are at risk to develop symptomatic and potentially severe hepatitis A.

Background: The malnutrition of the infants could be explained by a delay of the growth and the perturbation of biological parameters., Aim: To establish the nutritional profile of the Tunisian infant of less than two years. To specify the principal deficiencies and the possible origins of these deficiencies., Methods: In our transverse exploratory study, carried out in period of 9 month. This study was conducted in two groups of Tunisian young children less than two years old: a control group and a malnourished group (Z score < or = 2SD)., Results: Our data consolidate the important impact of pregnant women nutritional state and of breastfeeding on the foetus ant infant growth.Compared to control infants, the malnourished young showed a significant alteration of different biologic parameters. This alteration appeared positively linked to the gravity of malnutrition as indicated by the positive relation obtained between the weight/height ratio and many studied parameters. The malnourished infants showed, notably, a significant reduction of the average values of Chol-HDL, apo AI, Vit E, TSH and TF4 levels and Chol-HDL/Chol LDL ratio. Chol-HDL, apo AI and HDL/Chol-LDL are found positively and significantly correlated with TF4. So, their reduction in ill children would be, at least in part, a side effect of the thyroid function reduction., Conclusion: Our results confirm the existence of an important change of biological profile in malnourished young children. Besides, they emphasize that studies about young children could be helpful, notably, in the prevention and the fight against atherosclerosis.

Background: The fragile X syndrome was the most frequent etiology of hereditary mental retardation but the clinical diagnosis is not easy and the individual clinical symptoms were not specific so the confirmation will be made par molecular study of the gene of the fragile X syndrome. The aim of our study is to realise the molecular diagnosis of the fragile X syndrome in 200 Tunisian boys with mental retardation. Our results shows that the frequency of the fragile X syndrome is 7,6%. In the most cases there is a family history of mental retardation with medium age at 11 years. All the boys with the full mutation have mental retardation, dysmorphic features and macro-orchidism (pubescent boy), Conclusion: The screening of the molecular abnormalities of FMRI gene must be realised in every boy with mental retardation or boy with delayed speech without any identified etiology. The earlier diagnosis is important for genetic counselling.

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 patients, we established a relationship between chromosome anomalies and the clinical expression of TS, based on an analysis of stature and reproduction disorders. Short stature and primary amenorrhea were correlated with total deletion of one chromosome X or imbalanced gene dosage due to structural X anomalies. Whereas cases of infertility, recurrent miscarriages and secondary amenorrhea were associated with a mosaic karyotype pattern (45,X/46,XX or 45,X/46,XX/47,XXX ...), with a slight mosaicism in most cases. Thus, chromosome investigations should be performed in cases of reproduction failure even for women with normal stature.

Unlabelled: Mucopolysaccharidosis type I (MPS I) is a lysosomal disease due to mutations in the gene encoding alpha-l-iduronidase (IDUA) leading to variable clinical phenotypes with progressive severe organomegaly, bone and neurological involvement in the most severe forms. The aim of our study was to propose in Tunisia a strategy of molecular and prenatal diagnosis of the MPS I., Population and Methods: Our study was carried out on 8 MPS I patients recruited from different Tunisian regions and issued from 5 unrelated families. All the patients were offspring of consanguineous marriages., Results: The clinical and biological study led to diagnose 5 Hurler patients and 3 Hurler-Scheie patients. Three IDUA mutations were identified by molecular analysis within 6 different families: a novel mutation p.F602X and 2 already described mutations p.P533R and p.R628X., Discussion: MPS I is a heterogeneous disease characterized by variability of the phenotypes. The missense mutation p.P533R associated with the intermediate phenotype was the most frequent in the Tunisian but also in the Moroccan population. In Tunisia, the incidence of p.P533R mutation seems to be associated with the high frequency of consanguineous marriages., Conclusion: The identification of known MPS I mutations (p.P533R and p.R628X) and of the novel mutation p.F602X permits reliable genetic counselling of at-risk relatives and molecular prenatal diagnosis.

Background: Cirrhosis is rare in pediatrics. The children cirrhosis is particular by the ascendancy of biliairy cirrhosis and cirrhosis due to an innate error of metabolism and by the relative frequency of the cases where an etiological treatment is possible. However in developing countries, the children cirrhosis still put problems of etiological diagnosis and of therapeutic coverage., Aim: To study epidemiological and etiological particularities, therapeutic modalities and outcome of cirrhosis in the south of Tunisia., Methods: We led a retrospective study over 15 years (1990-2004) having allowed to depict 71 cirrhotic children followed in the service of general pediatric department of SFAX University hospital (Tunisia)., Results: Our patients divide up into 36 girls and 35 boys. The age of revelation of the disease was variable (15 days to 15 years). Jaundice and hepatomegaly were the most two clinical signs frequently found in the clinical exam. On the etiological plan, biliairy cirrhosis (Extra hepatic biliary atresia, dilatation of choledocal cyst, progressive familial intrahepatic cholestasis...) were the most frequent (40%) followed by metabolic cirrhosis(tyrosinemia type I, Wilson disease...) (17 %) and post-hepatitic cirrhosis (17%). In 27% of cases, no etiology was found. Besides the symptomatic treatment, an etiological treatment was tempted in some cases. No patient benefited from hepatic transplantation. The follow-up of the children cirrhosis was grave because 30 children (42%) died, 19 children are lost-sight and 22 children (31%) are still alive., Conclusion: The children cirrhosis pose still in our country of the problem of etiological diagnosis because of the not availability of some specific additional exams and especially problems of coverage for lack of a program of hepatic transplantation.

A Tunisian patient affected by mucopolysaccharidosis (MPS) was investigated for a biological analysis (quantitative and qualitative glycosaminoglycans (GAG) screening). We have also done an enzymatic determination of alpha-L-iduronidase activity (IDUA). The most common mutation (p.Gln 70 X, p.Trp 402X and p.Pro 533 Arg) were researched by an enzymatic restriction and sequencing of the IDUA gene. Enzymatic and urinary diagnostics suggested a MPS I phenotype. The patient investigated had the mutation p.Pro 533 Arg in the homozygous status, whereas his parents were heterozygous for this mutation.

Mucopolysaccharidosis type IV A (MPS IV A) is an autosomal recessive disorder resulting from the deficient activity of the lysosomal enzyme, N-acetylgalactosamine-6-sulfate sulfatase (GALNS) and the progressive lysosomal accumulation of keratane sulfate. Clinically, the MPS IV A differs from the other MPS by the localisation of the keratane sulfate in skelet and in eyes associated to the conservation of a normal intelligence. To date, the characterization and purification of the GALNS gene made a research for pathogenic mutations in patients with MPS IV A easier. These mutations are responsible of severe, intermediate or mild phenotype. The aim for this work was the research of clinical, biologic and molecular characteristics of two Tunisian MPS IV A patients who were offsprings of consanguineous mating. Enzymatic and urinary diagnostics suggested a MPS IV A phenotype. A novel homozygous mutation IVS1+1G-A was identified by direct sequencing in the GALNS gene of the two patients. Identification of GALNS mutations provide genotype/phenotype correlations and permit the precision of anomalies responsible of Morquio A phenotype in concerned families.

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 deleted in 58% (35/60) of patients (77% in type I (27/35), 27,7% in type II (5/18), 50% (3/6) in type III. No patient had a deletion in NAIP gene without a deletion in the SMN1 gene. Homozygous deletion of NAIP exon 5 was detected in 1 parent. Our results show that the incidence of NAIP deletion is higher in the more severe SMA cases.

Purpose: To study Bardet-Biedl syndrome (BBS) in the Tunisian population and determine the presence of triallelism in the eight identified BBS genes., Methods: DNA samples were collected from 19 consanguineous Tunisian families with BBS. Genome-wide scans were performed with microsatellite markers in 12 families, and two-point linkage analyses were performed. Direct sequencing was used to screen patients with BBS for mutations in all eight identified BBS genes., Results: Mutations in the BBS genes were identified in nine families. In addition, a large consanguineous family (57004) showed linkage to the BBS7 locus, although no mutation was identified. Five novel mutations were present in the nine families: one in BBS2 (c.565C>T, p.ArgR189Stop), one in BBS5 (c.123delA, p.Gly42GlufsX11), one in BBS7 (g.47247455&#95;47267458del20004insATA, p.Met284LysfsX7), and two in BBS8 (c.459+1G>A, p.Pro101LeufsX12 and c.355&#95;356insGGTGGAAGGCCAGGCA, p.Thr124ArgfsX43)., Conclusions: All families in which mutations were identified show changes in both copies of the mutant gene, and inheritance patterns in all families are consistent with autosomal recessive inheritance excluding any evidence of triallelism in the BBS genes in Tunisia.

Mucopolysaccharidosis type IVA (MPS IVA; OMIM #253000) or Morquio A syndrome is an autosomal recessive inborn error resulting from the deficient activity of the lysosomal enzyme, N-acetylgalactosamine-6-sulfatase (GALNS), and the progressive lysosomal accumulation of sulfated glycosaminoglycans. Clinically, the severe form of this lysosomal storage disease is characterized by a characteristic severe bone dysplasia and normal intelligence. To date, a variety of mutations have been associated with the severe MPS IVA phenotype. Here, we report the GALNS mutations in six severe MPS IVA patients from four unrelated Tunisian families. For mutation detection, each of the 14 exons and adjacent intron-exon junctions of the GALNS gene were sequenced after PCR-amplification from genomic DNA. Two novel mutations were identified: a G to A transition in the conserved 5' donor splice site of intron 1 (GACgt-->GACat: designated IVS1(+1g-->a)) and a G to C transversion in codon 66 of exon 2 predicting a glycine to arginine substitution (G66R). The IVS1(+1g-->a) mutation was homozygous in five similarly affected patients from three presumably unrelated families, but haplotype analysis suggested a common ancestor. The affected patient in the fourth family was homozygous for the G66R mutation. These are the first GALNS mutations causing severe MPS IVA disease identified in Tunisia. These molecular findings provide genotype/phenotype correlations, and permit accurate carrier detection, prenatal diagnosis, and counseling for MPS IVA disease in Tunisia where first cousin consanguineous mating remains frequent.

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.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease resulting from the defective activity of the enzyme alpha-L-iduronidase (IDUA). The disease has severe and milder phenotypic subtypes. The IDUA mutations in five MPS I patients from three unrelated families from central and southern Tunisia were determined by amplifying and sequencing each of the IDUA exons and intron-exon junctions. Two novel IDUA mutations, c.1805delTinsGAACA in exon 13 and I270S in exon 7, and two previously reported mutations, P533R and R628X, were detected. The two patients in family 1 who had the Hurler phenotype were homoallelic for the novel deletion-insertion mutation. The patient in family 2 who also had the Hurler phenotype was heteroallelic for the novel missense mutation I270S and the previously reported nonsense mutation R628X. The two patients in family 3 who had the Hurler-Scheie phenotype were homoallelic for P533R. In addition, six known IDUA polymorphisms were identified. These are the first Tunisian MPS I patients to be genotyped. The identification of these mutations and their genotype-phenotype correlations should facilitate prenatal diagnosis and counselling for MPS I in Tunisia, where a very high rate of consanguinity exists.

Aim: To evaluate the interest of IgA antibodies to tissue transglutaminase in the diagnosis of children coeliac disease compared with anti-endomysium and anti-gliadin antibodies., Subjects and Methods: Seventy children with coeliac disease (mean age: 5 years and 8 months) and 99 disease controls (mean age: 4 years and 5 months). IgA anti-transglutaminase were tested by ELISA using a human recombinant tissue transglutaminase. IgA anti-endomysium were detected by indirect immunofluorescence on monkey oesophagus., Results: The middle rate of IgA anti-transglutaminase was 101.06 units in patients and only 0.47 unit in controls. IgA anti-transglutaminase and IgA anti-endomysium were in agreement in 98.8% of cases; only two cases were discordant (+/- and -/+). Globally, the two markers had the same sensitivity (90%), specificity (98%), negative (93.2%) and positive (96.9%) predictive values. For anti-gliadin antibodies, the IgG were more sensitive (88.6%) and the IgA more specific (93.9%)., Conclusion: IgA anti-tissue transglutaminase can be used instead of IgA anti-endomysium as a serological marker of screening and diagnosis of coeliac disease in children after 3 years., (Copyright John Libbey Eurotext 2003.)

Cystic fibrosis was regarded a long time as exceptional in the Nord Africaine population and in particular in Tunisia what was at the origin of the ignorance of its various diagnostic and therapeutic aspects in our country. Nevertheless, with the development of the means of the diagnosis, several cases of cystic fibrosis were diagnosed these last years what will pose true problems of assumption of responsibility of these children like illustrates it well our experiment in the pediatric department of Sfax university hospital. In 10 years going of 1991 to 2000 we reported 7 cases of cystic fibrosis in the pediatric department of Sfax university hospital. Our patients are 3 boys and 4 girls. The age of revelation of the disease varied from 3 months to 14 years with 4 years and 10 months an average age. All our patients had a respiratory symptomatology in the foreground. The evolution was marked by the death of 4 patients at an average age of 5 years and half whereas the 3 surviving patients for the moment are more or less balanced on the nutritional level, digestive and respiratory. Cystic fibrosis is not exceptional in our area, its assumption of responsibility therapeutic is difficult, and it requires the collaboration of several experts and a good compliance of the child and of his family.

The mucopolysaccharidosis are hereditary diseases. The neurological attack constitutes the principal factor of gravity of these affections. We conducted a retrospective study over a period of 12 years (1988-1999) in the pediatric department of Sfax University Hospital. This study allowed us to observe 11 cases of mucopolysaccharidosis confirmed by an enzymatic proportioning, with 3 cases of Hurler disease (IH), 3 cases of the disease of sanfilippo, (two II A and one III B), 3 cases of the disease of Morquio A (type IVA) and 2 cases of the disease of Maroteaux Lamy (type VI). A sex ratio of 1.75. The parents were cousins in 90% of the cases. The age of revelation ranged between 6 months to 4 years. The clinical examination has found a staturo-pondral delay in 81.8% of the cases, a craniofacial dysmorphy in 100%, deformations of the rachis in 63.6% of the cases, a psychomotor regression in 54.5% of the cases, a medullary compression in 18% of the cases, hepatosplenomegaly in 36.4%, and corneal opacities in 45.4% of the cases. The therapeutic treatment was limited to the symptomatic measures with genetic consulting and antenatal diagnosis.

Sixty-three cases of anuria secondary to renal stones were treated in the Sfax urology department between 1982 and 1990. The presenting symptoms are frequently polymorphic and non-specific. The prognosis of these patients largely depends on the infectious complications associated with anuria, the delay in management and, most importantly, the course of preexisting renal failure. Fifteen deaths (24%) were observed in this series, despite emergency urinary diversion and appropriate treatment to eliminate the obstruction.

The authors report thirty-two cases of children with staghorn calculi treated in the department of urology H. Bourguiba, Hospital of Sfax. Such calculi are frequently seen in young boys over the age of 6 years. Urinary tract infection by Proteus is the main etiologic factor of lithogenesis. Surgical treatment, still the most advocated, is laborious; it must ensure complete stone removal, while protecting renal function.

A case of conjunctival dirofilariasis was reported in a 55 years old patient, from Kairouan. The human dirofilariasis comes always and only from animals. In most cases, the dirofilariasis is localised under the skin; the ocular localisation of the disease is rare or exceptional. The authors discuss the epidemiology and describe the possible ocular localisation of the dirofilariasis.

Between March 1982 and March 1986, 11 out of 72 patients (15%) undergoing chronic hemodialysis in a Tunisian hemodialysis unit developed septicaemia. The causative organism was a staphylococcus aureus in 8 patients, and the main portal of entry was the dialysis catheter (6/8). Septic pulmonary metastasis were observed in 3 cases. REmoval of the dialysis catheter and antibiotic therapy led to recovery in 7 cases. The 4 fatalities were attributed to respiratory failure in 3 cases and septic shock in one case. These results indicate that the prognosis of septicaemia in hemodialysis patients is poor.

Conjunctival lesions of ocular myiasis are common in the mediterranean region. The authors report 23 cases of conjunctival myiasis. This affection is caused by fly's larvae: Oestrus ovis presenting typically with inflamed and oedematous eyes. We diagnose the affection by directly showing the larvae on conjunctiva. The treatment consisted to extirpate larvae one by one.