Search

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_824del(p.Ser275Phefs*17) in SQSTM1 gene (GenBank: NM_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. [ABSTRACT FROM AUTHOR]

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]

We study graded star products on dual of finite dimensional Lie algebras. We prove that all graded star products are entirely determined by the expression of X * u where X belongs to the Lie algebra g and u is a polynomial function on the dual g* of g. We also consider the Hochschild cohomology and we prove that all graded differential star products are equivalent. [ABSTRACT FROM AUTHOR]

Limb girdle myopathies (LGM) form a group of clinically and genetically heterogeneous diseases responsible of progressive weakness predominantly affecting the shoulder and pelvic girdles muscles. Duchenne muscular dystrophy (DMD) and sarcoglycanopathies have been for decades recognized as the main myopathy's subtypes in Tunisia. We have performed a retrospective study including the patients diagnosed with LGM since January 2014 until December 2023, with an age onset of at least 2 years old. We have reviewed the full family history and medical data. All of the patients underwent CK levels dosage, EMG, muscle biopsy and molecular genetic studies. We excluded the patients diagnosed with DMD. We obtained a cohort of 44 patients, 60% of cases were males and 40% were females. Targeted genetic diagnosis of sarcoglycanopathies was performed in 50% of our patients. LGMDR5 was the most frequent subtype, with three identified variants of mutations in the SGCG gene: c521 del T (hot-spot mutation), c582 ins A and c525 del T. In the other half of our cohort, larger genetic analysis, with a LGMD panel or a whole exome sequencing (WES), showed mutations in the CAPN3 (LGMDR1), DYSF (LGMDR2), FKRP (LGMDR9), POMT1 (LGMDR11), GMPPB (LGMDR19), and COL6A1 (LGMDR22) genes. In addition, mutations in new genes that were not previously described in Tunisia were also identified: TITIN, RYR1, LMNA, GGPS1, PYROXD1, COL13A1 and VMA21. We emphasize the genetic variability of LGM in Tunisia and North Africa. The list of the implicated genes is continuously extending, exceeding so far the sarcoglycanopathies group. [ABSTRACT FROM AUTHOR]

Rigid spine syndrome is a classically childhood-onset progressive and non-painful limitation of the neck and trunk flexion leading to postural abnormalities. Myopathies related to mutations in EMD, LMNA, SEPN1, COL6 and FHL1 genes are the most frequent causes. We report the case of a 10-year-old boy, born of consanguineous Libyan parents, who presents since the age of 7 years difficulties in the neck extension and progressive spine straightness. Motor and intellectual development were normal. On examination he showed a cachectic phenotype, spontaneous trunk flexion, prominent rigid spine, scapular winging, and flat retracted thorax. We found no spontaneous limb joint contractures. Weakness was more prominent in the cervicodorsal spine, and mild in the proximal upper limb muscles. Amyotrophy involved preferentially neck, trunk, and deltoid muscles. The patient is ambulant; however, his sport performance was limited and often complains about excessive fatigue. Creatine kinase levels were normal, and EMG showed myogenic pattern. On the deltoid muscle biopsy, we found the presence of numerous nemaline bodies confirming the diagnosis of nemaline myopathy (NM). The whole exome sequencing revealed the presence of a homozygous variant in the Cofilin-2 (CFL2) gene, a rare cause of autosomal recessive NM. The variant we found: NM_021914.7:c.115T>G p.(Cys39Gly), is classified as a variant of uncertain significance (class 3) according to the recommendations of ACMG. However, we considered it as a potentially relevant result, since the CFL2 gene is reported essentially in patients with NM, and the presence of multiple nemaline bodies on the patient's muscle biopsy. [ABSTRACT FROM AUTHOR]

An oil obtained from the dried leaves of Lavandula stoechas L. in 0.77% yield was analyzed by capillary GC and GC/MS. Fenchone (68.2%) and camphor (11.2%) were the main components of the 28 identified molecules. This oil has been tested for antimicrobial activity against six bacteria, and two fungi. The results showed that this oil was active against all of the tested strains; Staphylococcus aureus was the more sensitive strain. [ABSTRACT FROM AUTHOR]

Abstract Background To identify the genetic defect associated with autosomal recessive congenital cataract (ARCC), mental retardation (MR) and ARCC, MR and microcephaly present in most patients in four Tunisian consanguineous families. Methods We screened four genes implicated in congenital cataract by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly. Among its three genes PAX6, PITX3 and HSF4 are expressed in human brain and one gene LIM2 encodes for the protein MP20 that interact with the protein galectin-3 expressed in human brain and plays a crucial role in its development. All genes were screened by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly. Results We report no mutation in the four genes of congenital cataract and its flanking regions. Only variations that did not segregate with the studied phenotypes (ARCC associated to MR, ARCC associated with MR and microcephaly) are reported. We detected three intronic variations in PAX6 gene: IVS4 -274insG (intron 4), IVS12 -174G>A (intron12) in the four studied families and IVS4 -195G>A (intron 4) in two families. Two substitutions polymorphisms in PITX3 gene: c.439 C>T (exon 3) and c.930 C>A (exon4) in one family. One intronic variation in HSF4 gene: IVS7 +93C>T (intron 7) identified in one family. And three intronic substitutions in LIM2 gene identified in all four studied families: IVS2 -24A>G (intron 2), IVS4 +32C>T (intron 4) and c.*15A>C (3'-downstream sequence). Conclusion Although the role of the four studied genes: PAX6, PITX3, HSF4 and LIM2 in both ocular and central nervous system development, we report the absence of mutations in all studied genes in four families with phenotypes associating cataract, MR and microcephaly.