Houweyda Jilani

Cholestasis is caused by genetic disorders in 25% of cases. Our study aimed to describe the clinical and genetic profile of cholestasis and to demonstrate the importance of next‐generation sequencing (NGS) in the etiologic diagnosis of genetic cholestasis. We included patients referred for cholestasis over a 10‐year period. Molecular studies using NGS consisted of a 292‐gene panel and/or whole exome sequencing. Our cohort included 70 patients from 66 unrelated families. A genetic diagnosis was established in 70% of the families. The most common diagnoses were Type 2 progressive familial intrahepatic cholestasis ( n = 12), neonatal sclerosing cholangitis ( n = 4), low phospholipid‐associated cholelithiasis syndrome ( n = 4), and Alagille syndrome ( n = 4). The ABCB11 gene was most frequently mutated (15/46), with two recurrent variants, c.1062T>A (p.Tyr354*) and c.1826_1827dup (p.Ile610Glnfs*45), found in six and four families, respectively. Our results showed a 62% diagnostic yield of molecular testing using NGS in cholestasis. An accurate diagnosis was key to providing appropriate genetic counseling, guiding screening of variant carriers, and prenatal diagnosis.

Gaucher disease (GD) is a rare metabolic disorder due to pathogenic variants in the GBA gene. We report the first case of the rare p.Arg87Trp pathogenic variant (formerly known as R48W) of the GBA gene in the Tunisian population. A female Arab patient was assessed at the age of 26 due to abdominal distension, bone pain, and headache since she was 25. Physical examination revealed splenomegaly, rib deformation, lumbar scoliosis, and upper limb tremor. Bone marrow was infiltrated by Gaucher cells. The patient was homozygous for the rare p.Arg87Trp variant which is known to be associated with a mild phenotype. This report highlights the necessity of screening the Tunisian population for this rare variant.

Dyskeratosis congenital (DC) is the first genetic syndrome described among telomeropathies. Its classical phenotype is characterized by the mucocutaneous triad of reticulated pigmentation of skin lace, nail dystrophy and oral leukoplakia. The clinical presentation, however, is heterogeneous and serious clinical complications include bone marrow failure, hematological and solid tumors. It may also involve immunodeficiencies, dental, pulmonary and liver disorders, and other minor complication. Dyskeratosis congenita shows marked genetic heterogeneity, as at least 14 genes are responsible for the shortening of telomeres characteristic of this disease. This review discusses clinical characteristics, molecular genetics, disease evolution, available therapeutic options and differential diagnosis of dyskeratosis congenita to provide an interdisciplinary and personalized medical assessment that includes family genetic counseling.