The First Case of Huntington's Disease like 2 in Mali, West Africa.

Background: Huntington's disease like 2 (HDL2) has been reported exclusively in patients with African ancestry, mostly originating from South Africa. Case report: We report three patients in Mali including a proband and his two children who have been examined by neurologists and psychiatrists after giving consent. They were aged between 28 and 56 years old. Psychiatric symptoms were predominant in the two younger patients while the father presented mainly with motor symptoms. Genetic testing identified a heterozygous 40 CTG repeat expansion in the Junctophilin-3 (JPH3) gene in all three patients. Discussion: This study supports the hypothesis that HDL2 may be widely spread across Africa. Highlights: We report here the first case of HDL2 in West Africa, suggesting that HDL2 is widely spread across African continent, and increasing access to genetic testing could uncover other cases.

A case of Huntington disease-like 2 in a patient of African ancestry: the everlasting support of clinical examination in the molecular era.

Chorea, cognitive decline, and psychiatric symptoms are shared by Huntington's disease (HD) and similar conditions called HD phenocopies. We describe the first case reported in Italy of Huntington disease-like 2 (HDL2), clinically and radiologically indistinguishable from HD, showing the importance of considering African ancestry in the diagnostic process.

Methylation­associated inactivation of JPH3 and its effect on prognosis and cell biological function in HCC.

In recent years, researchers have found that epigenetics plays an important role in the occurrence and development of hepatocellular carcinoma (HCC). DNA methylation is involved in the proliferation and metastasis of HCC. However, the junctophilin 3 (JPH3) level and the potential regulatory mechanism of its DNA methylation in HCC remain uncertain. In the present study, 73 HCC samples were enrolled to analyze the expression of JPH3. Reverse­transcription quantitative PCR, western blotting and immunohistochemistry were used to detect the expression of JPH3 in HCC. Kaplan­Meier method and Cox regression analysis were applied to evaluate the prognostic impact of JPH3 on HCC patients. DNA methylation­specific PCR and bisulfite Sanger sequencing were used to detect the degree of DNA methylation of JPH3 in HCC. The demethylation drug 5­Aza­2'­deoxycytidine (5­Aza) was used to reduce the DNA methylation of JPH3. The role of JPH3 in the malignant biological behavior of HCC by promoting epithelial­mesenchymal transition (EMT) was confirmed by functional cell experiments. The results showed that JPH3 exhibited low levels in HCC tissues and cell lines. HCC patients with low expression of JPH3 had poor survival outcomes. JPH3 had higher DNA methylation levels in HCC tissues and cell lines. When the demethylation drug 5­Aza was used to reduce the degree of methylation of JPH3, its protein expression level was significantly increased and it significantly inhibited the malignant biological behavior of HCC cells. Additionally, effective increase in the expression of JPH3 through gene regulation technology also inhibited the proliferation, invasion and migration of HCC cells. After altering the DNA methylation level of JPH3, the EMT of HCC cells was also affected. Therefore, our study demonstrated the inactivation of JPH3 by promoter methylation and its function as a tumor suppressor in HCC. JPH3 may serve as a biomarker for early diagnosis and as a potential therapeutic target for HCC.

The Neuropsychiatry of Huntington Disease-Like 2: A Comparison with Huntington's Disease.

BACKGROUND: Huntington Disease-Like 2 (HDL2) is a rare autosomal dominant disorder caused by an abnormal CAG/CTG triplet repeat expansion on chromosome 16q24. The symptoms of progressive decline in motor, cognitive and psychiatric functioning are similar to those of Huntington's disease (HD). The psychiatric features of the HDL2 have been poorly characterized. OBJECTIVE: To describe the neuropsychiatric features of HDL2 and compare them with those of HD. METHODS: A blinded cross-sectional design was used to compare the behavioural component of the Unified Huntington's Disease Rating Scale (UHDRS) in participants with HDL2 (n = 15) and HD (n = 13) with African ancestry. RESULTS: HDL2 patients presented with psychiatric symptoms involving mood disturbances and behavioural changes that were not significantly different from those in the HD group. Duration of disease and motor performance correlated (p < 0.001) with the Functional Capacity score and the Independence score of the UHDRS. HD patients reported movement dysfunction as the first symptom more frequently than HDL2 Patients (p < 0.001). CONCLUSION: The psychiatric phenotype of HDL2 is similar to that of HD and linked to motor decline and disease duration. Psychiatric symptoms seem more severe for HDL2 patients in the early stages of the disease.

Macrocerebellum, epilepsy, intellectual disability, and gut malrotation in a child with a 16q24.1-q24.2 contiguous gene deletion.

Macrocerebellum is a rare condition characterized by enlargement of the cerebellum with conservation of the overall shape and cytoarchitecture. Here, we report on a child with a distinctive constellation of clinical features including macrocerebellum, epilepsy, apparent intellectual disability, dysautonomia, gut malrotation, and poor gut motility. Oligonucleotide chromosome microarray analysis identified a 16q24.1-q24.2 deletion that included four OMIM genes (FBXO31, MAP1LC3B, JPH3, and SLC7A5). Review of prior studies describing individuals with similar or overlapping16q24.1-q24.2 deletions identified no other reports of macrocerebellum. These observations highlight a potential genetic cause of this rare disorder and raise the possibility that one or more gene(s) in the 16q24.1-q24.2 interval regulate cerebellar development.