Cytogenetic and molecular diagnosis of Fanconi anemia revealed two hidden phenotypes: Disorder of sex development and cerebro-oculo-facio-skeletal syndrome.

BACKGROUND: Several studies have shown a high rate of consanguinity and endogamy in North African populations. As a result, the frequency of autosomal recessive diseases is relatively high in the region with the co-occurrence of two or more diseases. METHODS: We report here on a consanguineous Libyan family whose child was initially diagnosed as presenting Fanconi anemia (FA) with uncommon skeletal deformities. The chromosome breakage test has been performed using mitomycin C (MMC) while molecular analysis was performed by a combined approach of linkage analysis and whole exome sequencing. RESULTS: Cytogenetic analyses showed that the karyotype of the female patient is 46,XY suggesting the diagnosis of a disorder of sex development (DSD). By looking at the genetic etiology of FA and DSD, we have identified p.[Arg798*];[Arg798*] mutation in FANCJ (OMIM #605882) gene responsible for FA and p.[Arg108*];[Arg1497Trp] in EFCAB6 (Gene #64800) gene responsible for DSD. In addition, we have incidentally discovered a novel mutation p.[Gly1372Arg];[Gly1372Arg] in the ERCC6 (CSB) (OMIM #609413) gene responsible for COFS that might explain the atypical severe skeletal deformities. CONCLUSION: The co-occurrence of clinical and overlapping genetic heterogeneous entities should be taken into consideration for better molecular and genetic counseling.

Clinical and Genetic Characterization of 26 Tunisian Patients with Allgrove Syndrome.

BACKGROUND AND AIMS: Allgrove syndrome is characterized by achalasia, alacrima, and adrenal insufficiency as well as being associated with progressive neurological signs. This is an autosomal recessive disorder due to mutations in the AAAS gene located on chromosome 12q13. The AAAS gene encodes a protein of 546 amino acids, ALADIN. Mutations in this genwere reported in families from North Africa and Europe. Our objective is to conduct a clinical, molecular and genetic study of 26 Tunisian patients with Allgrove syndrome. METHODS: We report 26 Tunisian patients with between two and four clinical features associated with Allgrove syndrome. Blood samples were collected and isolated DNA derived from subjects was amplified. The entire sequence of the AAAS gene was analyzed by PCR and sequencing. PCR-RFLP method was performed to identify the frequent mutations found. RESULTS: Sequencing of the AAAS gene revealed a major homozygous mutation (c.1331+1G>A) in 25 patients and R286X mutation in one patient. The presence of a major mutation in several unrelated affected individuals suggests the presence of a founder effect in Tunisia and allows for a fast and targeted molecular diagnosis. CONCLUSIONS: We created an easy and rapid molecular enzymatic protocol based on PCR-RFLP using MvaI restriction enzyme that directly targets this major mutation and can be used for prenatal diagnosis and genetic counseling for Tunisian families at risk. To the best of our knowledge, this is the first major series report of Allgrove syndrome in Tunisia.

New food from a potato somatic hybrid: nutritional equivalence and safety assessment by a feeding study on rats.

BACKGROUND: Potato tubers from the STBd somatic hybrid line that exhibited improved tolerance to salinity and resistance to fungal and PVY infections were characterised. They were compared for their chemical composition to the Spunta variety produced by conventional agronomic practices. This study aimed to compare nutritional value and safety by feeding rats with STBd or commercial tubers added to the standard diet (20/80 w/w). RESULTS: The analysis of soluble sugar, fat, fibre and ash content of tubers did not reveal any significant differences between the hybrid line and the control Spunta variety. Small differences were observed in dry matter, starch and protein content of hybrid potatoes in comparison to controls. However, all values were within normal ranges reported in the literature. The feeding study on rats showed that overall health, weight gain, food consumption, morphological aspects and weights of organs were comparable between rat groups fed the STBd hybrid and the Spunta variety. CONCLUSION: Taken together, 28 days of consumption of STBd hybrid potato did not exert any adverse effect on rats compared with commercial Spunta potato. The STBd potato line was therefore considered to be as safe for food utilisation as the commercial variety.

Ciprofloxacin-induced crystal nephropathy.

Ciprofloxacin is a commonly used antibiotic. Renal side effects are rare and are usually immune mediated. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of crystal nephropathy in a young woman treated with ciprofloxacin and a nonsteroidal anti-inflammatory drug.

Efficiency and midgut histopathological effect of the newly isolated Bacillus thuringiensis KS δ-endotoxins on the emergent pest Tuta absoluta.

Tuta absoluta (Povolny, 1994) is a devastating moth to the Solanaceae plants. It is a challenging pest to control, especially on tomatoes. In this work, we studied the entomopathogenic activity of the Cry-forming δ-endotoxins produced by Bacillus thuringiensis strain KS and B. thuringiensis kurstaki reference strain HD1 against T. absoluta. These strains carried the cry2, cry1Ab, cry1Aa / cry1Ac, and cry1I genes, and KS also carried a cry1C gene. The δ-endotoxins of KS were approximately twofold more toxic against the third instar larvae than those of HD1, as they showed lower 50% and 90% lethal concentrations (0.80 and 2.70 µg/cm² (δ-endotoxins/tomato leaf)) compared with those of HD1 (1.70 and 4.50 µg/cm²) (p < 0.05). Additionally, the larvae protease extract showed at least six caseinolytic activities, which activated the KS and HD1 δ- endotoxins, yielding the active toxins of about 65 kDa and the protease-resistant core of about 58 kDa. Moreover, the histopathological effects of KS and HD1 δ-endotoxins on the larvae midgut consisted of an apical columnar cell vacuolization, microvillus damage, and epithelial cell disruption. These results showed that the KS strain could be a candidate for T. absoluta control.

[Lafora disease: histopathological study of axillary cutaneous biopsy]. / Maladie de Lafora : étude histopathologique d'une biopsie cutanée axillaire.

Lafora body disease is a common and severe form of progressive myoclonic epilepsy. It is an autosomal recessive disorder with a gene locus recently mapped to chromosome 6q23-27. The disease presents between the age of 10 and 18 years with generalised seizures followed by myoclunus. Intellectual deterioration occurs early and progresses to dementia. The diagnosis must be usually confirmed by demonstrating Lafora bodies. The practical procedure is the axillary skin biopsy that shows PAS positive inclusion in the cells of the sweet ducts. We present a case of Lafora disease discovered in a 26-year-old man. Moreover, we emphasize on the diagnosis difficulties of this disease.

A rare cause of Dysphagia in a pregnant woman:herpes simplex esophagitis.

Herpes simplex esophagitis (HSE) has rarely been reported in immunocompetent individuals. In a search of Medline until October 2012, we found only one case of HSE in a pregnant female. We present the first case of HSE in a healthy 36-year-old female at 27 weeks gestation who recovered without antiviral therapy.

Letter: Intestinal heterotopia in urethral caruncle.

We report a case of urethral caruncle with intestinal heterotopia in a 26-year-old woman. This entity is rarely reported.

Steroid 21-hydroxylase gene mutational spectrum in 50 Tunisian patients: characterization of three novel polymorphisms.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease of steroid biosynthesis in humans. More than 90% of all CAH cases are caused by mutations of the 21-hydroxylase gene (CYP21A2), and approximately 75% of the defective CYP21A2 genes are generated through an intergenic recombination with the neighboring CYP21A1P pseudogene. In this study, the CYP21A2 gene was genotyped in 50 patients in Tunisia with the clinical diagnosis of 21-hydroxylase deficiency. CYP21A2 mutations were identified in 87% of the alleles. The most common point mutation in our population was the pseudogene specific variant p.Q318X (26%). Three novel single nucleotide polymorphism (SNP) loci were identified in the CYP21A2 gene which seems to be specific for the Tunisian population. The overall concordance between genotype and phenotype was 98%. With this study the molecular basis of CAH has been characterized, providing useful results for clinicians in terms of prediction of disease severity, genetic and prenatal counseling.

Poor prognostic factors of lupus nephritis.

The occurrence of renal involvement during the clinical course of systemic lupus erythematous (SLE) is generally considered to be the most important factor influencing the prognosis in terms of morbidity and mortality. The factors influencing prognosis in lupus nephritis (LN) are variable in literature. Our aim was to determine predictive factors of poor prognosis in LN among our population. In this retrospective study, 82 cases of LN observed over 18 years were studied. There were 12 males and 70 females with a mean age of 26.9 ± 11 years. At presentation, the mean proteinuria was 3.9 ± 4 g/day; the nephrotic syndrome, hematuria, leukocyturia and renal failure were observed in 67.1%, 63.4%, 56.1% and 37.8% of cases, respectively. LN was of class I, II, III, IV and V in 4.9%, 13.4%, 23.2%, 50% and 8.5% of the cases, respectively. Fifteen patients developed end-stage renal failure and/or died. The presence of hypertension, renal failure, massive proteinuria and high activity index score of LN was associated with poor renal prognosis.

[Abrikosoff's tumor: a clinicopathologic study of nine cases]. / Tumeur d'Abrikosoff : etude anatomoclinique de neuf cas.

BACKGROUND: Abrikossoff's tumour or granular cell tumor or is a benign neurogenic tumour. It is ubiquitous with the most frequently affected site is the head and neck region. AIMS: To report a series of granular cell tumors and to discuss its clinicopathologic features and histogenesis. METHODS: We report a series of nine cases diagnosed between January 2004 and December 2006 in the Pathology Department of the University Hospital of Sfax. We have collected the clinical aspects and we have proceeded on a pathological, cytochemical (PAS and PAS diastasis) and immunohistochemical study. RESULTS: Nine cases of TCG are presented: 5 females and 4 males. The median age was 33.9 years (extremes: 7 and 53 years). All tumours were unique. The most common localization was in the head and neck region (5 cases). The diagnosis was suspected using standard histologic criteria and confirmed by immunohistochemistry: tumour cells expressed vimentine (90%), S100 protein (100%) and neuron specifique enolase (80%). In all cases patients were treated by excisional resection and had a benign course with no evidence of recurrence (median follow up: 2 years). CONCLUSION: Granular cell tumours are rare neoplasm which must be recognised because they demonstrate a benign behaviour after their surgical excision. Histological features of granular cell tumours are commonly characteristic but some times they can be misdiagnosed as malignant tumours especially when the biopsy is superficial. The staining for neurogen markers and PAS are useful tools.

Mucinous tubular and spindle cell carcinoma of the kidney associated with tuberculosis.

Mucinous tubular and spindle cell carcinomas (MTSCC) are low-grade renal epi-thelial neoplasms with approximately 100 documented cases reported in the literature. We report a case of MTSCC in a 79-year-old patient in association with a renal tuberculosis infection that has never been reported. Further investigations are needed to determine the frequency and true prognosis of these tumors.

[Ewing sarcoma osseous and extraosseous : a clinicopathologic study of 29 cases]. / Sarcome d'Ewing Osseux et Extra Osseux : Etude anatomo-clinique de 29 cas.

BACKGROUND: Ewing's sarcoma (ES) is a rare tumour accounting for 10% of primary malignant bone tumours in children and 3% of all childhood malignancies. ES belongs to a group of small round cell tumours. AIM: In this review, we will describe the main clinicopathological features of this rare tumour and discuss its prognosis. METHODS: We report a retrospective study of 29 cases of ES, of which 4 were extraosseous, diagnosed over a period 11 years (January 1989 - December 1999). Clinicopathological data were described. Hematoxylin-eosin staining and immunohistochemical study were reviewed. RESULTS: 12 patients were male and 17 were female (ratio: 0,8) with a median age of 16 years. 62,5% of tumours were located in flat bone and 33,3% in long bone. The medium size of the tumor was 10,6 cm (range:3-25cm). 27,5% of patients presented with metastatic disease at time of diagnosis. Microscopically, tumour tissue was composed of round, small, blue cells with fine granular chromatin. Tumour cells strongly coexpressed CD99 and vimentin (100%). Systemic treatment consisted of adjuvant chemotherapy (84,2%). Local control was based on and surgery (57,9%) or radiation therapy (36,8%). A good response to chemotherapy was obtained in 37.5%; 13,7% of patients were alive without disease (medium follow up: 169 mois); 34,5% of patients developed metastases (medium follow up : 23 months) and 10,3% developed recurrences (medium follow up :13 months). CONCLUSION: Our study emphasizes two points : the great size of the tumor and the frequent location in flat bone which may explain the poor prognosis of Ewing sarcoma in our series despite the multidisciplinary treatment.