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1.
Clin Rheumatol ; 41(5): 1359-1369, 2022 May.
Article in English | MEDLINE | ID: mdl-35028743

ABSTRACT

BACKGROUND: An association between ANXA1, FPR1 and FPR2 gene polymorphisms and the patho-physiology of many human diseases was suggested by numerous studies. OBJECTIVE: Our study aimed to evaluate association between common polymorphisms in the 9q21.13 and 19q13.41 and susceptibility to systemic lupus erythematosus (SLE) in the Tunisian population. MATERIALS: We performed a case-control study on 107 Tunisian SLE patients and 122 healthy controls to explore 9 polymorphisms of the three studied genes: rs2811226 and rs3739959 (ANXA1), rs5030880, rs1042229, rs1461765570, rs17849971, rs867228 (FPR1), rs17694990 and rs11666254 (FPR2). RESULTS: Four polymorphisms were found to be linked with SLE susceptibility: rs3739959-ANXA1 > G and GG (p = 0.021, OR = 1.73 and p = 0.014, OR = 2.06 respectively), rs867228-FPR1 > TT (p = 0.014, OR = 4.59), rs11666254-FPR2 > GG (p = 0.019, OR = 8.34) and rs17694990-FPR2 > T (p = 0.05, OR = 1.506). In homogenous groups of SLE patients depending on clinical manifestations and serological results, previous associations were confirmed with a panoply of manifestations of lupus including lupus nephritis, malar rash, mouth ulceration and hypocomplementia. CONCLUSION: Our study showed an association between ANXA1 > rs3739959, FPR1 > rs867228, FPR2 > rs11666254, FPR2 > rs17694990 and SLE susceptibility. Our results also showed a strong association between the two ANXA1 studied SNPs and LN which allowed us to suggest these two SNPs as biomarkers of LN development in SLE. Further research is needed to understand by which mechanism the gene variants affect susceptibility to SLE. Key Points • Lupus erythematosus is an autoimmune disease in which a panoply of factors are implicated • Annexin A1 interaction with its receptors are suggested as a target in therapy of a panoply of human disease in particular cancers • The present results highlighted the implication of Annexin A1 and its receptors gene polymorphisms in the physiopathology of lupus, in particular in the involvement of renal and cutaneous lesions.


Subject(s)
Annexin A1 , Lupus Erythematosus, Systemic , Annexin A1/genetics , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/genetics , Male , Polymorphism, Single Nucleotide
2.
J Adv Res ; 31: 13-24, 2021 07.
Article in English | MEDLINE | ID: mdl-34194829

ABSTRACT

Introduction: Hearing impairment (HI) is characterized by complex genetic heterogeneity. The evolution of next generation sequencing, including targeted enrichment panels, has revolutionized HI diagnosis. Objectives: In this study, we investigated genetic causes in 22 individuals with non-GJB2 HI. Methods: We customized a HaloplexHS kit to include 30 genes known to be associated with autosomal recessive nonsyndromic HI (ARNSHI) and Usher syndrome in North Africa. Results: In accordance with the ACMG/AMP guidelines, we report 11 pathogenic variants; as follows; five novel variants including three missense (ESRRB-Tyr295Cys, MYO15A-Phe2089Leu and MYO7A-Tyr560Cys) and two nonsense (USH1C-Gln122Ter and CIB2-Arg104Ter) mutations; two previously reported mutations (OTOF-Glu57Ter and PNPT1-Glu475Gly), but first time identified among Tunisian families; and four other identified mutations namely WHRN-Gly808AspfsX11, SLC22A4-Cys113Tyr and two MYO7A compound heterozygous splice site variants that were previously described in Tunisia. Pathogenic variants in WHRN and CIB2 genes, in patients with convincing phenotype ruling out retinitis pigmentosa, provide strong evidence supporting their association with ARNSHI. Moreover, we shed lights on the pathogenic implication of mutations in PNPT1 gene in auditory function providing new evidence for its association with ARNSHI. Lack of segregation of a previously identified causal mutation OTOA-Val603Phe further supports its classification as variant of unknown significance. Our study reports absence of otoacoustic emission in subjects using bilateral hearing aids for several years indicating the importance of screening genetic alteration in OTOF gene for proper management of those patients. Conclusion: In conclusion, our findings do not only expand the spectrum of HI mutations in Tunisian patients, but also improve our knowledge about clinical relevance of HI causing genes and variants.


Subject(s)
Hearing Loss/diagnosis , Hearing Loss/genetics , Adult , Child, Preschool , Deafness/diagnosis , Deafness/genetics , Exoribonucleases , Female , Genetic Heterogeneity , Genetic Testing/methods , High-Throughput Nucleotide Sequencing/methods , Humans , Male , Membrane Proteins , Mutation , Mutation, Missense , Pedigree , Phenotype , Tunisia , Usher Syndromes/diagnosis , Usher Syndromes/genetics , Young Adult
3.
Am J Med Genet A ; 185(4): 1081-1090, 2021 04.
Article in English | MEDLINE | ID: mdl-33403770

ABSTRACT

Pathogenic variants in Steroid 5 alpha reductase type 3 (SRD5A3) cause rare inherited congenital disorder of glycosylation known as SRD5A3-CDG (MIM# 612379). To date, 43 affected individuals have been reported. Despite the development of various dysmorphic features in significant number of patients, facial recognition entity has not yet been established for SRD5A3-CDG. Herein, we reported a novel SRD5A3 missense pathogenic variant c.460 T > C p.(Ser154Pro). The 3D structural modeling of the SRD5A3 protein revealed additional transmembrane α-helices and predicted that the p.(Ser154Pro) variant is located in a potential active site and is capable of reducing its catalytic efficiency. Based on phenotypes of our patients and all published SRD5A3-CDG cases, we identified the most common clinical features as well as some recurrent dysmorphic features such as arched eyebrows, wide eyes, shallow nasal bridge, short nose, and large mouth. Based on facial digital 2D images, we successfully designed and validated a SRD5A3-CDG computer based dysmorphic facial analysis, which achieved 92.5% accuracy. The current work integrates genotypic, 3D structural modeling and phenotypic characteristics of CDG-SRD5A3 cases with the successful development of computer tool for accurate facial recognition of CDG-SRD5A3 complex cases to assist in the diagnosis of this particular disorder globally.


Subject(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , Abnormalities, Multiple/genetics , Cataract/genetics , Congenital Disorders of Glycosylation/genetics , Membrane Proteins/genetics , Muscular Atrophy/genetics , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/ultrastructure , Abnormalities, Multiple/pathology , Adolescent , Cataract/complications , Cataract/pathology , Child , Child, Preschool , Congenital Disorders of Glycosylation/complications , Congenital Disorders of Glycosylation/pathology , Eye/pathology , Facial Recognition , Facies , Female , Humans , Membrane Proteins/ultrastructure , Muscular Atrophy/complications , Muscular Atrophy/pathology , Mutation, Missense/genetics
4.
J Child Neurol ; 29(1): 49-53, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23275435

ABSTRACT

We to report clinical biological and radiologic features of rubella encephalitis in childhood and assess its prognostic impact. Our retrospective study was conducted in an intensive care unit of a university hospital in Sfax, Tunisia. Twenty-one children (age range, 1-15 years) were included. Median age was 9 years (lower and upper quartiles, 7-11 years). On admission, generalized maculopapular eruption was found in 17 cases (81%). Median Glasgow Coma Scale score was 7 (lower and upper quartiles, 7-8). Twenty patients (95.2%) experienced at least 1 episode of seizures. Sixteen patients (76.2%) developed a status epilepticus. The result for enzyme-linked immunosorbent assay detecting anti-rubella immunoglobulin (M) was positive in the serum and in the cerebrospinal fluid samples for all our patients. Magnetic resonance imaging (MRI) of the brain was performed on admission for 3 patients (14.3%) and within a median of 4 days (lower and upper quartiles, 2-6 days) for 8 patients. The test was normal in 6 cases. Two deaths were recorded (9.5%). Survivors had no neurological sequelae 6 months after intensive care unit discharge.


Subject(s)
Encephalitis, Viral , Rubella , Treatment Outcome , Acyclovir/therapeutic use , Adolescent , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antibodies, Viral/cerebrospinal fluid , Antiviral Agents/therapeutic use , Brain/pathology , Brain/virology , Cefotaxime/therapeutic use , Child , Child, Preschool , Dexamethasone/therapeutic use , Encephalitis, Viral/diagnosis , Encephalitis, Viral/etiology , Encephalitis, Viral/therapy , Female , Follow-Up Studies , Humans , Infant , Intensive Care Units , Male , Retrospective Studies , Rubella/complications , Rubella/diagnosis , Rubella/therapy , Tunisia
5.
Int J Infect Dis ; 17(12): e1225-8, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24094525

ABSTRACT

OBJECTIVE: The aim of this study was to describe the epidemiological characteristics of Acinetobacter baumannii ventilator-associated pneumonia (VAP) and to identify factors predictive of a poor outcome. METHODS: A retrospective study was conducted over 16 months in a Tunisian intensive care unit (ICU). All adult patients with A. baumannii VAP were included. RESULTS: Ninety-two patients were included in they study; 41 (44.6%) were admitted because of multiple trauma. The mean age of the patients was 44.5±19.5 years. All patients needed mechanical ventilation on admission. The mean SAPS II score was 39±15. The mean delay before VAP onset was 8.1±4.7 days. On VAP onset, 57 patients (62%) developed septic shock. Only 14.2% of isolated strains were susceptible to imipenem; none were resistant to colistin. The mean duration of mechanical ventilation was 20±11 days. The mean duration of ICU stay was 24.3±18.7 days. ICU mortality was 60.9%. In the multivariate analysis, factors predictive of a poor outcome were previously known hypertension (odds ratio 5.8, 95% confidence interval 1.4-24.9; p=0.018) and VAP-related septic shock (odds ratio 8.5, 95% confidence interval 3-23.7; p<0.001). CONCLUSION: A. baumannii VAP is associated with a high mortality. Hemodynamic impairment is predictive of a poor outcome.


Subject(s)
Acinetobacter Infections/epidemiology , Acinetobacter baumannii/isolation & purification , Pneumonia, Ventilator-Associated/epidemiology , Pneumonia, Ventilator-Associated/microbiology , Acinetobacter Infections/diagnosis , Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Female , Follow-Up Studies , Hospital Mortality , Humans , Intensive Care Units , Male , Microbial Sensitivity Tests , Middle Aged , Odds Ratio , Pneumonia, Ventilator-Associated/diagnosis , Pneumonia, Ventilator-Associated/drug therapy , Prognosis , Retrospective Studies , Treatment Outcome , Tunisia/epidemiology , Young Adult
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