Elevated 4R‐tau in astrocytes from asymptomatic carriers of the MAPT 10+16 intronic mutation

X-linked Emery–Dreifuss muscular dystrophy (EDMD1) affects approximately 1:100,000 male births. Female carriers are usually asymptomatic but, in some cases, they may present clinical symptoms after age 50 at cardiac level, especially in the form of conduction tissue anomalies. The aim of this study was to evaluate the relation between heart involvement in symptomatic EDMD1 carriers and the X-chromosome inactivation (XCI) pattern. The XCI pattern was determined on the lymphocytes of 30 symptomatic and asymptomatic EDMD1 female carriers—25 familial and 5 sporadic cases—seeking genetic advice using the androgen receptor (AR) methylation-based assay. Carriers were subdivided according to whether they were above or below 50 years of age. A variance analysis was performed to compare the XCI pattern between symptomatic and asymptomatic carriers. The results show that 20% of EDMD1 carriers had cardiac symptoms, and that 50% of these were ≥50 years of age. The XCI pattern was similar in both symptomatic and asymptomatic carriers. Conclusions: Arrhythmias in EDMD1 carriers poorly correlate on lymphocytes to a skewed XCI, probably due to (a) the different embryological origin of cardiac conduction tissue compared to lymphocytes or (b) the preferential loss of atrial cells replaced by fibrous tissue.

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BG09: A homozygous intronic mutation in UNC13D in type 3 familial haemophagocytic lymphohistiocytosis: pathogenic insights regarding subcutaneous panniculitis‐like T‐cell lymphoma

British Journal of Dermatology ◽

10.1111/bjd.20168 ◽

2021 ◽

Vol 185 (S1) ◽

pp. 71-71

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Haemophagocytic Lymphohistiocytosis ◽

Intronic Mutation ◽

Type 3 ◽

Familial Haemophagocytic Lymphohistiocytosis

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The dynamics of fractional order Hepatitis B virus model with asymptomatic carriers

Alexandria Engineering Journal ◽

10.1016/j.aej.2021.02.057 ◽

2021 ◽

Vol 60 (4) ◽

pp. 3945-3955

Author(s):

Nadia Gul ◽

Rubi Bilal ◽

Ebrahem A. Algehyne ◽

Maryam G. Alshehri ◽

Muhammad Altaf Khan ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Fractional Order ◽

Asymptomatic Carriers ◽

B Virus ◽

Virus Model

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Novel deep intronic mutation in PLA2G6 causing early-onset Parkinson’s disease with brain iron accumulation through pseudo-exon activation

Neurogenetics ◽

10.1007/s10048-021-00667-0 ◽

2021 ◽

Author(s):

Chiara Cavestro ◽

Celeste Panteghini ◽

Chiara Reale ◽

Alessia Nasca ◽

Silvia Fenu ◽

...

Keyword(s):

Early Onset ◽

Cerebellar Atrophy ◽

Iron Accumulation ◽

Brain Iron ◽

Causative Gene ◽

Coding Regions ◽

Aberrant Transcript ◽

Pathogenic Variants ◽

Intronic Mutation ◽

Mrna Analysis

AbstractPLA2G6 is the causative gene for a group of autosomal recessive neurodegenerative disorders known as PLA2G6-associated neurodegeneration (PLAN). We present a case with early-onset parkinsonism, ataxia, cognitive decline, cerebellar atrophy, and brain iron accumulation. Sequencing of PLA2G6 coding regions identified only a heterozygous nonsense variant, but mRNA analysis revealed the presence of an aberrant transcript isoform due to a novel deep intronic variant (c.2035-274G > A) leading to activation of an intronic pseudo-exon. These results expand the genotypic spectrum of PLAN, showing the paramount importance of detecting possible pathogenic variants in deep intronic regions in undiagnosed patients.

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PIN51 Role of Asymptomatic Carriers in the Transmission of COVID-19: A Review

Value in Health ◽

10.1016/j.jval.2021.04.1239 ◽

2021 ◽

Vol 24 ◽

pp. S114-S115

Author(s):

U. Abubakar ◽

M. Hammad

Keyword(s):

Asymptomatic Carriers

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Genetic parkinsonisms and cancer: a systematic review and meta-analysis

Reviews in the Neurosciences ◽

10.1515/revneuro-2020-0083 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Andrea Sturchio ◽

Alok K. Dwivedi ◽

Joaquin A. Vizcarra ◽

Martina Chirra ◽

Elizabeth G. Keeling ◽

...

Keyword(s):

Head And Neck ◽

Meta Analysis ◽

Head And Neck Cancers ◽

Breast Cancers ◽

Asymptomatic Carriers ◽

Skin Cancers ◽

Prostate Cancers ◽

Meta Analyses ◽

Genetic Contributions ◽

Nonmelanoma Skin Cancers

AbstractGenes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay remains unclear. We systematically reviewed studies (PubMed 1967–2019) reporting gene variants associated with both parkinsonism and cancer. Somatic variants were examined in cancer samples, whereas germline variants were examined in cancer patients with both symptomatic and asymptomatic (carriers) genetic parkinsonisms. Pooled proportions were calculated with random-effects meta-analyses. Out of 9,967 eligible articles, 60 were included. Of the 28 genetic variants associated with parkinsonism, six were also associated with cancer. In cancer samples, SNCA was predominantly associated with gastrointestinal cancers, UCHL1 with breast cancer, and PRKN with head-and-neck cancers. In asymptomatic carriers, LRRK2 was predominantly associated with gastrointestinal and prostate cancers, PRKN with prostate and genitourinary tract cancers, GBA with sarcoma, and 22q11.2 deletion with leukemia. In symptomatic genetic parkinsonism, LRRK2 was associated with nonmelanoma skin cancers and breast cancers, and PRKN with head-and-neck cancers. Cancer was more often manifested in genetic parkinsonisms compared to asymptomatic carriers. These results suggest that intraindividual genetic contributions may modify the co-occurrence of cancer and neurodegeneration.

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