Phenotypic intrafamilial variability including H syndrome and Rosai–Dorfman disease associated with the same c.1088G > A mutation in the SLC29A3 gene

Background Mutations in the SLC29A3 gene, which encodes the nucleoside transporter hENT3, have been implicated in syndromic forms of histiocytosis including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, Faisalabad histiocytosis and Familial Rosai–Dorfman disease (RDD). Herein, we report five new patients from a single family who present with phenotypes that associate features of H syndrome and Familial Rosai–Dorfman disease. Methods We investigated the clinical, biochemical, histopathological and molecular findings in five Tunisian family members' diagnosed with Familial RDD and/or H syndrome. The solute carrier family 29 (nucleoside transporters), member 3 (SLC29A3) gene was screened for molecular diagnosis using direct Sanger sequencing. Results Genetic analysis of all affected individuals revealed a previously reported missense mutation c.1088 G > A [p.Arg363Gln] in exon 6 of the SLC29A3 gene. Four affected members presented with clinical features consistent with the classical H syndrome phenotype. While their cousin’s features were in keeping with Familial Rosai–Dorfman disease diagnosis with a previously undescribed cutaneous RDD presenting as erythematous nodular plaques on the face. This report underlines the clinical variability of SLC29A3 disorders even with an identical mutation in the same family. Conclusion We report a rare event of 5 Tunisian family members' found to be homozygous for SLC29A3 gene mutations but showing a different phenotype severity. Our study reveals that despite a single mutation, the clinical expression of the SLC29A3 disorders may be significantly heterogeneous suggesting a poor genotype–phenotype correlation for the disease.

Phenotypic intrafamilial variability including H syndrome and Rosai Dorfman Disease associated with the same c.1088G>A mutation in the SLC29A3 gene.

Background: Mutations in the SLC29A3 gene, which encodes the nucleoside transporter hENT3, has been implicated in syndromic forms of Histiocytosis including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, Faisalabad histiocytosis and Familial Rosai Dorfman disease (RDD). Herein, we report five new patients from a single family who present with phenotypes that associate features of H syndrome and Familial Rosai Dorfman Disease.Methods: We investigated the clinical, biochemical, histopathological and molecular findings in five Tunisian family Members' diagnosed as Familial RDD and/or H syndrome. The solute carrier family 29 (nucleoside transporters), member 3 ( SLC29A3 ) gene was screened for molecular diagnosis using direct Sanger sequencing.Results: Genetic analysis of all affected individuals revealed a previously reported missense mutation c.1088 G>A [p.Arg363Gln] in exon 6 of the SLC29A3 gene. Four affected members presented with clinical features consistent with classical H syndrome phenotype. While their cousin’s features were in keeping with the diagnosis of Familial Rosai Dorfman disease with a previously undescribed cutaneous RDD presenting as erythematous nodular plaques on the face. This report underlines the clinical variability of SLC29A3 disorders even with an identical mutation in the same family.Conclusion: We report a rare event of 5 Tunisian family Members' found to be homozygous for SLC29A3 gene mutations but showing a different phenotype severity. Our study reveals that despite a single mutation, the clinical expression of the SLC29A3 disorders may be significantly heterogeneous suggesting a poor genotype-phenotype correlation for the disease.

Dynamics of Conflicts in Family Firms: Towards a Non-Linear Approach to the Succession Process

The succession process can be a traumatic event in the life cycle of a family firm and is usually characterised by an increased interest towards the firm of the successor accompanied by a progressive disengagement of the predecessor. Drawing on five longitudinal case studies of Tunisian family firms examined from 2016 to 2019, we investigated the sequential and dynamic nature of this process, focusing on the conflicts among family members involved in the process. The main findings suggest that professional and family-related conflicts can lead to excessive tensions between the involved parties, which can result in failure of the succession process. Moreover, specific contingency factors, such as tragic events, can positively or negatively trigger deviation from the succession process path.

Phenotypic Intrafamilial Variability Including H Syndrome and Rosai Dorfman Disease Associated With the Same c.1088G>A mutation in the SLC29A3 gene.

BackgroundMutations in the SLC29A3 gene, which encodes the nucleoside transporter hENT3, has been implicated in syndromic forms of Histiocytosis including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, Faisalabad histiocytosis and Familial Rosai Dorfman disease (RDD). Herein, we report five new patients from a single family who present with phenotypes that associate features of H syndrome and Familial Rosai Dorfman Disease.MethodsWe investigated the clinical, biochemical, histopathological and molecular findings in five Tunisian family Members' diagnosed with Familial RDD and/or H syndrome. The solute carrier family 29 (nucleoside transporters), member 3 (SLC29A3) gene was screened for molecular diagnosis using direct Sanger sequencing.ResultsGenetic analysis of all affected individuals revealed a previously reported missense mutation c.1088 G>A [p.Arg363Gln] in exon 6 of the SLC29A3 gene. Four affected members presented with clinical features consistent with the classical H syndrome phenotype. While their cousin’s features were in keeping with the diagnosis of Familial Rosai Dorfman disease with a previously undescribed cutaneous RDD presenting as erythematous nodular plaques on the face. This report underlines the clinical variability of SLC29A3 disorders even with an identical mutation in the same family.ConclusionWe report a rare event of 5 Tunisian family Members' found to be homozygous for SLC29A3 gene mutations but showing a different phenotype severity. Our study reveals that despite a single mutation, the clinical expression of the SLC29A3 disorders may be significantly heterogeneous suggesting a poor genotype-phenotype correlation for the disease.

Identification of Novel BRCA1 Germline Deleterious Variant Among a Tunisian Family

Inherited predisposition to breast and ovarian cancer are most frequently due to germline mutations in the main genes BRCA1 (OMIM# 113705) and BRCA2 (OMIM# 600185). These inactivating mutations, essentially frameshift and nonsense variation, occurs mainly across conserved regions. The aim of the present study is to report a novel germline BRCA1 mutation identified in a Tunisian family case with early onset of breast and ovarian cancer and to evaluate the genotype phenotype correlation. The proband had high-grade tumors, invasive unilateral ductal carcinoma developed at the age of 38 and a serous ovarian adenocarcinoma after a gap of twelve years. The molecular analysis revealed a novel heterozygous nonsense BRCA1 mutation NM_007294.4: c.915T>A p.(C305*) in the proband and her daughter. This mutation leads to a truncated protein which pathogenicity was validated by bioinformatics tools. This variant is subject to nonsense-mediated mRNA decay. We also underlined the immunohistochemistry usefulness by lack of expression of BRCA1 protein in paraffin embedded breast tumor contrasting with normal tissue. Clinical and pathological data tend to be homogeneous and led to the conclusion that there is a genotype phenotype correlation in BRCA1, an element that must be taken into account in genetic counselling. Conclusively, we are the first to report this novel BRCA1 germline likely deleterious variant extending the molecular and clinical spectrum of BRCA1 pathogenic point mutations. Further in vitro functional experiments needs to be established. High-risk individuals carrying this BRCA1 mutation benefit from preventive measures to reduce morbidity.

TINJAUAN SOSIO-POLITIK TERHADAP LARANGAN POLIGAMI (Pembaharuan Hukum Keluarga Tunisia)

The practice of polygamy which is carried out by some Tunisian society generally torments the wife. This is the basis for the prohibition of polygamy in Tunisia. The purpose of this research is to find out about the prohibition of polygamy in Tunisia which is contained in the Tunisian Family Law. This study uses literature research that focuses on the object of study on existing books and literature. While the method used in this research is descriptive-analysis method, which provides an overview and analyzes the Tunisian family law regarding the prohibition of polygamy. The results of this study indicate that the Tunisian State in implementing the law on the prohibition of polygamy cannot be separated from social politics. The factor is the number of husbands who torment their wives and children. This is one of the reasons that makes the law on the prohibition of polygamy come into effect. Because of the injustice committed by husbands to their wives. But in reality the regulations on the prohibition of polygamy are still not running optimally. This is because there is no common will between the government and the people. Abstrak Praktek poligami yang dilakukan oleh sebagian masyarakat Tunisia pada umumnya menyengsarakan pihak isteri. Inilah yang menjadi dasar pelarangan Poligami di Tunisia. Tujuan penelitian ini adalah mencari tau terhadap pelarangan poligami di Negara Tunisia yang termuat dalam Hukum Keluarga Tunisia. Penelitian ini menggunakan penelitian kepustakaan yang memfokuskan pada objek kajian pada buku-buku dan literature yang ada. Sedangkan metode yang digunakan dalam penelitian ini adalah metode deskriptif-analisis, yaitu memberikan gambaran dan menganalisis Hukum Keluarga Tunisia terkait tentang pelarangan poligami. Hasil dari penelitian ini menunjukkan bahwa Negara Tunisia dalam penerapan undang-undang tentang larangan poligami tidak lepas dari social politik. Faktornya ialah dengan banyaknya para suami yang menyengsarakan pihak isteri dan anak. Inilah salah satu penyebab yang menjadikan berlakunya perundang-undangan tentang larangan poligami. Karena ketidakadilan yang dilakukan suami terhadap para isterinya. Tetapi pada kenyataannya peraturan larangan poligami tersebut berjalan masih belum maksimal. Ini disebabkan karena tidak adanya kesamaan kehendak antara pemerintah dan masyarakat.

Whole genome sequencing and phylogenetic classification of Tunisian SARS-CoV-2 strains from patients of the Military Hospital in Tunis

In the present work, two complete genome sequences of SARS-CoV-2 were obtained from nasal swab samples of Tunisian SARS-CoV-2 PCR-positive patients using nanopore sequencing. The virus genomes of two of the patients examined, a Tunisian soldier returning from a mission in Morocco and a member of another Tunisian family, showed significant differences in analyses of the total genome and single nucleotide polymorphisms (SNPs). Phylogenetic relationships with known SARS-CoV-2 genomes in the African region, some European and Middle Eastern countries and initial epidemiological conclusions indicate that the introduction of SARS-CoV-2 into Tunisia from two independent sources was travel-related.