Dyskeratosis congenita is a rare hereditary disease that occurs predominantly in males and manifests clinically as the classic triad of reticulate hyperpigmentation, nail dystrophy and leukoplakia. It increases the risk of malignancy and other potentially lethal complications such as bone marrow failure, lung and liver diseases. Mutations in 19 genes are associated with dyskeratosis congenita, and a fifth of the pathogenic mutations are found in DKC1, the gene coding for dyskerin. This review aims to address the clinical and genetic aspects of the disease.

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Bazex-Dupré-Christol syndrome is a rare genodermatosis that manifests with the classical triad of basal cell carcinoma, follicular atrophoderma, and hypotrichosis; yet it may be accompanied by milia, ichthyosis, neurological symptoms, and visceral malignancies. Symptom onset is nonsimultaneous, and hence the diagnosis is often made late and the opportunity of counseling and following up is missed. This article aims toward providing a comprehensive review of the clinical perspective of Bazex-Dupré-Christol syndrome, highlighting the major clinical variants to facilitate reaching a prompt diagnosis. In addition, the molecular aspects are discussed. Though the gene responsible for this syndrome is yet nonspecified, it is confirmed to be localized to the long arm of chromosome X.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system with genetics and environmental determinants. Studies focused on the neurogenetics of MS showed that mitochondrial DNA (mtDNA) mutations that can ultimately lead to mitochondrial dysfunction, alter brain energy metabolism and cause neurodegeneration. We analyzed the whole mitochondrial genome using next-generation sequencing (NGS) from 47 Saudi individuals, 23 patients with relapsing-remitting MS and 24 healthy controls to identify mtDNA disease-related mutations/variants. A large number of variants were detected in the D-loop and coding genes of mtDNA. While distinct unique variants were only present in patients or only occur in controls, a number of common variants were shared among the two groups. The prevalence of some common variants differed significantly between patients and controls, thus could be implicated in susceptibility to MS. Of the unique variants only present in the patients, 34 were missense mutations, located in different mtDNA-encoded genes. Seven of these mutations were not previously reported in MS, and predicted to be deleterious with considerable impacts on the functions and structures of encoded-proteins and may play a role in the pathogenesis of MS. These include two heteroplasmic mutations namely 10237T>C in MT-ND3 gene and 15884G>C in MT-CYB gene; and three homoplasmic mutations namely 9288A>G in MT-CO3 gene, 14484T>C in MT-ND6 gene, 15431G>A in MT-CYB gene, 8490T>C in MT-ATP8 gene and 5437C>T in MT-ND2 gene. Notably some patients harboured multiple mutations while other patients carried the same mutations. This study is the first to sequence the entire mitochondrial genome in MS patients in an Arab population. Our results expanded the mutational spectrum of mtDNA variants in MS and highlighted the efficiency of NGS in population-specific mtDNA variant discovery. Further investigations in a larger cohort are warranted to confirm the role of mtDNA MS.

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Dyskeratosis congenita is a rare hereditary disease that occurs predominantly in males and manifests clinically as the classic triad of reticulate hyperpigmentation, nail dystrophy and leukoplakia. It increases the risk of malignancy and other potentially lethal complications such as bone marrow failure, lung and liver diseases. Mutations in 19 genes are associated with dyskeratosis congenita, and a fifth of the pathogenic mutations are found in DKC1, the gene coding for dyskerin. This review aims to address the clinical and genetic aspects of the disease.

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