Cytogenetic assessment of Fanconi anemia in children with aplastic anemia in Tunisia.

BACKGROUND: Chromosome breakage hypersensitivity to alkylating agents is the gold standard test for Fanconi anemia (FA) diagnosis. The aim of the present study was to assess the proportion of FA cases among aplastic anemia (AA) in Tunisian pediatric patients. OBSERVATION: Investigation of mitomycin C-induced chromosomal breakage was carried out in 163 pediatric patients with AA and siblings of the cases where diagnosis of FA was confirmed. We identified 31 patients with FA whose percentage of unstable mitoses ranges from 65% to 100%. Among 18 siblings who were investigated for chromosomal instability, 3 were incidentally found to be affected. CONCLUSIONS: FA is an important cause of AA in Tunisia. Our report is the first study in North Africa that explored cytogenetic and phenotypic findings in FA children. It also showed the importance of mitomycin C sensitivity screening in all FA siblings.

Identification and characterization of a new Leishmania major specific 3'nucleotidase/nuclease protein.

We report the characterization of a new Leishmania major gene, lmaj3'nt/nu, encoding a 382 amino acids protein, Lmaj3'NT/NU, that belongs to the 3'nucleotidase/nuclease family. Interestingly, sequence and phylogenetic analysis show that this protein is Leishmania major specific and thus constitutes a new 3'nucleotidase/nuclease subgroup. Lmaj3'NT/NU displays nuclease enzymatic activity and Western blot analysis shows that it is exclusively expressed in promastigotes. Immunofluorescence microscopy using a specific anti-Lmaj3'NT/NU shows that the protein has a plasma membrane localization. Surprisingly, contrary to the previously described Leishmania mexicana 3'NT/NU, lmaj3'nt/nu is not up-regulated when parasites are cultured under purine starvation conditions. Together, these findings suggest Lmaj3'NT/NU may constitute a new important compound of the L. major purine scavenging pathway and could be involved in sandfly parasite survival and colonization.

Characteristic pattern of chromosomal imbalances in posttransplantation lymphoproliferative disorders: correlation with histopathological subcategories and EBV status.

BACKGROUND: Posttransplantation lymphoproliferative disorders (PTLDs) are a spectrum of lymphoid proliferations, occurring in immunosuppressed organ transplant recipients. They comprise early lesions, polymorphic (P-PTLD), monomorphic (M-PTLD), and Hodgkin/Hodgkin-like lymphoma PTLD (HL-PTLD) lesions. Most of them are associated with Epstein-Barr virus (EBV). Little is known about their genetic changes. MATERIALS AND METHODS: We have studied 35 PTLDs[7 P-PTLDs (3/7 polyclonal IgH), 26 M-PTLDs (22 B-cell PTLD, 4 T-cell PTLD), 2 HL-PTLDs], using comparative genomic hybridization (CGH), a DNA-based technique allowing a screening of chromosomal imbalances without needing cultured cells. RESULTS.: Overall incidence of chromosomal imbalances: 51.5 %. The most frequent gains involved 8q24, 3q27 [4 cases each]; 2p24p25, 5p, 9q22q34, 11, 12q22q24, 14q32, 17q, 18q21 [2 cases each]. Nonrandom losses were 17p13 [4 cases]; 1p36, 4q [3 cases each]; 17q23q25, Xp [2 cases each]. Three high-level amplifications were detected: 4p16, 9p22p24, 18q21q23. In this latter imbalance, involvement of Bcl2 has been confirmed by FISH. The nonrandom CGH imbalances occurring in M-PTLD are usually described in lymphomas of immunocompetent patients and contain genes known to be involved in lymphomagenesis, while genomic abnormalities detected in half cases of EBV positive P-PTLD are mostly unknown. CONCLUSION: This study reported nonrandom chromosomal imbalances in PTLD and also identified early genomic alterations in EBV positive P-PTLD. These results raise two questions: the role of such lesions in the development and progression of those EBV induced-lymphoproliferations and their clinical significance especially in P-PTLD.

Multiple congenital anomalies/mental retardation syndrome with multiple circumferential skin creases: a new syndrome?

We describe a combination of multiple congenital anomalies, a severe psychomotor retardation and seizures in a 9-year-old Tunisian boy with circumferential ringed skin creases. He had symmetrical circumferential skin creases on arms, legs, and penis. Craniofacial anomalies included: an elongated face, tight forehead, hypertelorism, bilateral epicanthic folds, upslanting palpebral fissures, microphthalmia, convergent strabismus, wide nasal bridge, aberrant teeth, dental caries, and low-set posteriorly rotated ears with overfolded thick helices. He had also ureterocele, hypospadias, and others anomalies. The magnetic resonance imaging of the brain showed hypoplastic vermis, hypoplastic corpus callosum, and dilatation of ventricles. Chromosomal analysis revealed a normal male karyotype with 46,XY. Skin biopsy was normal. To the best of our knowledge, this combination of anomalies has not been reported and this case may be a unique syndrome.