Cole disease is a genodermatosis of pigmentation following a strict dominant mode of inheritance. In this study, we investigated eight patients affected with an overlapping genodermatosis after recessive inheritance. The patients presented with hypo- and hyperpigmented macules over the body, resembling dyschromatosis universalis hereditaria in addition to punctuate palmoplantar keratosis. By homozygosity mapping and whole-exome sequencing, a biallelic p.Cys120Arg mutation in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was identified in all patients. We found that this mutation, like those causing dominant Cole disease, impairs homodimerization of the ENPP1 enzyme that is mediated by its two somatomedin-B-like domains. Histological analysis revealed structural and molecular changes in affected skin that were likely to originate from defective melanocytes because keratinocytes do not express ENPP1. Consistently, RNA-sequencing analysis of patient-derived primary melanocytes revealed alterations in melanocyte development and in pigmentation signaling pathways. We therefore conclude that germline ENPP1 cysteine-specific mutations, primarily affecting the melanocyte lineage, cause a clinical spectrum of dyschromatosis, in which the p.Cys120Arg allele represents a recessive and more severe form of Cole disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO) of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population.

BackgroundGiardia duodenalis is a common human intestinal parasite worldwide, and the causative agent of diarrhea, with the severity of disease ranging from asymptomatic to intense and debilitating infection. G. duodenalis is known to consist of eight genetically distinct assemblages, named from A to H. No data available on the genotypes and genetic diversity of G. duodenalis circulating in Qatar.MethodsWe genotyped 54 human Giardia isolates, collected from asymptomatic immigrants in Qatar, using a multilocus genotyping (MLGs) tool. We also investigated relationships between the subjects’ genotypes and their demographic data.ResultsGenomic DNA from 54 isolates were tested by PCR and sequence analysis at three loci: glutamate dehydrogenase (gdh), β-giardin (bg) and triose phosphate (tpi)). Assemblage A was identified in nine (16.67%), assemblage B in thirty (55.55%), and a mixture of assemblages A+B in fifteen (27.78%) isolates. All assemblage A isolates, genotyped in different loci, were assigned to sub-assemblage AII, and six of them had MLGs AII-1 while one new MLG was identified in two isolates. Sequences of assemblage B isolates have high level of genetic diversity and high presence of heterogeneous peaks, especially within the gdh gene. No significant associations between genotypes and the immigrants’ demographic data were found due to the extensive number of new variants.ConclusionsMLGs was used herein to genotype 54 immigrant Giardia isolates. The high level of genetic variability found in our isolates hampered MLGs determination, more investigations are now required to consolidate our findings, and to enable a comprehensive understanding of the diversity within G. duodenalis assemblage B isolates.

We concluded that in glioblastoma, MGMT promoter methylation predicts TMZ sensitivity. This current comparative analysis leads to consider that MS-MLPA is a valuable as HM450 K array for MGMT methylation status screening.

Beckwith–Wiedemann syndrome has a wide spectrum of complications such as embryonal tumors, namely adrenocortical tumor. Tumor predisposition is one of the most challenging manifestations of this syndrome. A 45-day old female with a family history of adrenocortical tumor presented with adrenocortical tumor. The case raised suspicion of a hereditary Beckwith–Wiedemann syndrome, therefore molecular analysis was undertaken. The results revealed partial KCNQ1OT1 hypomethylation in the infant's blood DNA which was associated with a complete loss of methylation in the infant's adrenocortical tumor tissue. It is unique for familial Beckwith–Wiedemann syndrome caused by KCNQ1OT1 partial hypomethylation to manifest solely through adrenocortical tumor. Incomplete penetrance and specific tissue mosaicism could provide explanations to this novel hereditary Beckwith–Wiedemann syndrome presentation.

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