Hemoglobin A and Heterogeneous Diagnostic Relevance Observed in Eight New Variants of the Delta Globin Gene.

Background: Hemoglobin A (Hb A) (αβ) in the normal adult subject constitutes 96-98% of hemoglobin, and Hb F is normally less than 1%, while for hemoglobin A (Hb A) (αδ), the normal reference values are between 2.0 and 3.3%.

Clinical exome sequencing is a powerful tool in the diagnostic flow of monogenic kidney diseases: an Italian experience.

Background: A considerable minority of patients on waiting lists for kidney transplantation either have no diagnosis (and fall into the subset of undiagnosed cases) because kidney biopsy was not performed or histological findings were non-specific, or do not fall into any well-defined clinical category. Some of these patients might be affected by a previously unrecognised monogenic disease.

Methods: Through a multidisciplinary cooperative effort, we built an analytical pipeline to identify patients with chronic kidney disease (CKD) with a clinical suspicion of a monogenic condition or without a well-defined diagnosis.

A putative frameshift variant in the CHM gene is associated with an unexpected splicing alteration in a choroideremia patient.

Background: Due to the limited availability of mRNA analysis data, the number of exonic variants resulting in splicing impairment is underestimated although aberrant splicing correction is a promising therapeutic option to treat monogenic diseases, including choroideremia (CHM), a rare X-linked eye disorder arising from sequence alteration of the CHM gene. Herein we report an exonic frameshift variant associated with an mRNA splicing alteration that leads to a CHM hypomorphic allele.

Methods: Total RNA and genomic DNA were extracted from peripheral blood of a patient affected by a mild form of CHM.

Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes.

Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1-TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified.

Novel GRN Mutations in Alzheimer's Disease and Frontotemporal Lobar Degeneration.

Background: During the twentieth century, frontotemporal dementia (FTD) was often misdiagnosed, confused with Alzheimer's disease or psychiatric disorders, jeopardizing care and research.

Objective: To analyze the FTD genes in the DNA samples of patients belonging to families clinically classified as probable Alzheimer's disease (FAD) in the early 1990s and not carrying mutation in the three main genes linked to FAD (Presenilin 1, Presenilin 2, and Amyloid precursor protein).

Methods: The genetic screening was performed on 63 probands diagnosed as FAD before the early 2000s.