Lesch Nyhan syndrome: A novel complex mutation in a Tunisian child

Lesch Nyhan syndrome (LNS) is an X-linked recessive disorder due to complete deficiency of the hypoxanthine–guanine phosphoribosyltransferase (HPRT) enzyme. Defect of the enzymatic activity is related to mutations of the HPRT1 gene. The disorder severity is due to neurological features and renal complications. Up to now, more than 300 mutations have been reported. We report on a Tunisian child with a severe phenotype due to a novel identified complex mutation.     

Immunohistochemical analysis of c-erbB-2, Bcl-2, p53, p21WAF1/Cip1, p63 and Ki-67 expression in hydatidiform moles

Hydatidiform moles (HM) are characterized by an abnormal proliferating trophoblast with a potential for a malignant transformation. Similar to other human tumors, trophoblastic pathogenesis is likely a multistep process involving several molecular and genetic alterations. The study was performed to investigate the expression patterns of c-erbB-2 and Bcl-2 oncoproteins, p53, p21^WAF1/CIP1 and p63 tumor suppressor proteins and Ki-67 cell proliferation marker in HM.We conducted a retrospective study of 220 gestational products, including 39 hydropic abortions (HA), 41 partial HM (PHM) and 140 complete HM (CHM). The expression of c-erbB-2, Bcl-2, p53, p21^WAF1/CIP1, p63 and Ki-67 was investigated by immunohistochemistry on archival tissues. c-erbB-2 expression was observed in three PHM and 10 CHM. Bcl-2 immunostaining was significantly higher in PHM (61%) and CHM (70.7%) compared with HA (7.7%, p?=? 0.001 and p?<? 0.0001, respectively). p53 expression was stronger in CHM (73.6%) compared with PHM (24.4%, p < 0.0001) and HA (12.8%, p < 0.0001). p21^WAF1/CIP1 staining was observed as well in molar and non-molar gestations (p?>? 0.05). p63 immunoexpression was significantly described in CHM (85.7%) and PHM (78%) compared with HA (10.2%, p < 0.0001 and p = 0.0001, respectively). Ki-67 was significantly expressed in CHM (72.1%) compared with HA (46.2%, p = 0.005).Altered expression of Bcl-2, p53, p63 and Ki-67 reflects the HM pathological development. Immunohistochemical analysis is beneficial to recognize the HM molecular and pathogenic mechanisms. Furthermore, it could serve as a useful adjunct to conventional methods for refining HM diagnosis.     

Association between RANTES polymorphisms and asthma severity among Tunisian children

The chemokine known as RANTES (regulated upon activation, normal T cells expressed and secreted) is an important element for the chemotaxis at the site of allergic inflammation. Many studies have made an interesting link between RANTES polymorphisms and asthma, showing that the variant in the promoter region is associated with high risk of asthma and severe airway obstruction. We conducted a case-control and family study aiming at identifying the relationship between polymorphisms (-28 C/G and -403 G/A) and haplotypes in the RANTES gene with asthma and severity. The results of the case control study suggest an association between alleles level of -28 C/G and -403 G/A promoter polymorphism (p = 0.01) (p = 0.00175) and asthma. Univariate analysis of the RANTES polymorphisms show an increased prevalence of the AC and AG haplotypes in asthmatics (p = 0.014) and (p = 0.015) respectively. Our data suggest that -28 C/G and -403 G/A polymorphisms within the RANTES promoter region play an important role in asthma predisposition and in the severity of airway obstruction.     

Epidemiologic profile of Haemophilus influenzae infection in Tunisia

Haemophilus influenzae, a commensal bacteria, is frequently incriminated in broncho--pulmonary surinfections and severe diseases as meningitis, pneumonia and septic arthritis, particularly in young children. A multicenter study was conducted to establish the epidemiological profile of Haemophilus influenzae diseases, to determine the rate of antibiotics resistance for guide therapeutic and preventive strategies. The identification was based on the requirements for X and V factors, and the serotype b determined by agglutination. The betalactamase production was done by nitrocefin test. Antimicrobial susceptibility testing was determined on Muller Hinton chocolate agar with isovitalex. During the two year period, (January 1998 December 1999), 192 isolates of H. Influenzae were collected, 61% were recovered from invasive infections (44 meningitis, 8 bacteremia, 2 arthritis). The serotype b was identified in 55.7% of cases, 67.3% were invasive strains. 24.5% of isolates were producing betalactamase particularly invasive serotype b strains. All isolates of H. influenzae were susceptible to cefotaxim and to ofloxacin. Resistance rates to other antibiotics were: erythromycin 56.2%, tetracyclin 10.3%, rifampin 12%, chloramphénicol 1%, cotrimoxazole 16.5%, 11.5% amikacin and 20% gentamicin. The incidence of meningitis remained frequent in our country, involving the introduction of the vaccination in official calendar. Nevertheless, the surveillance of H. influenzae invasives infections and the serotyping of isolates were necessary to evaluate the impact of the immunization.     

Rapid Occurrence of Giant Left Ventricular Pseudoaneurysm after Mitral Valve Replacement

Left ventricular pseudoaneurysms are an uncommon and frightening complication after mitral valve replacement. We report the case of a 54‐year old woman, having undergone a mitral valve replacement with uneventful postoperative course and normal echocardiographic predischarge control, who was readmitted to hospital, only 16 days later, for rapidly progressing dyspnea, and finally echocardiographically diagnosed to have a massive 8‐cm long pseudoaneurysm communicating with the left ventricle through a narrow communication. The patient was proposed for emergency surgery but unfortunately died preoperatively.     

HLA- A, B, DR and DQ alleles study in Tunisian patients with atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from the interaction between envirommental and genetic factors. Many genes are involved in the etiopathology of AD, such as HLA genes. OBJECTIVES: Study the association between HLA-A, B, DR and DQ genes and the AD. METHODS: HLA A and B genotyping were practised for 53 atopic dermatitis patients and 76 healthy controls using the microlymphotoxicity complement dependent technique, while HLA DR and DQ genetyping were practised for only 20 patients with AD and all the controls by PCR-SSP method. RESULTS: Allelic frequency of HLA A32 was significantly increased in healthy individuals compared to patients affected with AD (p = 0.02, RR = 0.24). HLA-B, DR and DQ showed no differences in distrubition between patients and controls. CONCLUSION: Our study suggested that HLA-A32 could be a protective marker against atopic dermatitis for Tunisian patients, in contrast to HLA-B, DR and DQ alleles which seemed to have no importance in AD pathogenis.     

Chromosomal microarray analysis of functional Xq27-qter disomy and deletion 3p26.3 in a boy with Prader-Willi like features and hypotonia

Duplications of the long arm of the X chromosome are rare. The infantile phenotype shares some resemblance with the Prader-Willi syndrome, presenting severe psychomotor retardation, facial dysmorphic features with a broad face, a small mouth and a thin pointed nose, hypotonia, urogenital malformation and proneness to infections. We report a boy with an additional Xq27-qter chromosome segment translocated onto the short arm of chromosome 3. The karyotype was 46,XY,der(3)t(X;3)(q27.3; p26.3)mat. This cryptic unbalanced X-autosome translocation resulted in Xq27-qter functional disomy and a deletion 3p26.3. A detailed analysis of the constitutional chromosomal changes in the patient was performed using array-CGH, FISH and PCR. The aim was to characterize the size and the location of the duplication Xq27-qter (8.18 Mb) and of the deletion 3p26.3 (1.05 Mb), to establish phenotype-genotype correlations and to offer genetic counselling.