Renal cell carcinomas (RCCs) are the most common malignant tumor in Von Hippel-Lindau (VHL) disease, which is an inherited, autosomal dominant syndrome manifested by a variety of benign and malignant tumours. The major treatment is protect as much renal function as possible while avoiding metastasis. However, proper operative strategies are unclear. Therefore, we tracked the […]
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The Contribution of Spurious Transcription to Intellectual Disability Disorders
During embryonic development, the different cell types that make our bodies activate distinct gene expression programs. But what happens when the mechanisms that regulate cell-specific gene expression fail and the cells start to express genes that should be silenced? This is a typical feature of cancer cells often associated with genomic instability. Our article proposes […]
Associations of CDH1 germline variant location and cancer phenotype in families with hereditary diffuse gastric cancer (HDGC)
Hereditary diffuse gastric cancer (HDGC) is a cancer predisposition syndrome with significantly elevated life-time risks of gastric and breast cancer due to loss-of-function (LOF) germline variants of the CDH1 gene. There is considerable variability across affected families in its clinical manifestations including age-of-onset and cancer phenotype. In this study, we identified associations between location of […]
Diagnosis of ‘possible’ mitochondrial disease: an existential crisis
Primary mitochondrial diseases remain difficult to diagnose. Many patients with a phenotype concerning for mitochondrial disease are unable to receive genetic confirmation. In these instances, diagnostic terms such as “unlikely,” “possible” or “probable” mitochondrial disease are often used. Advances in genomic testing have shown that some patients with a clinical phenotype and biochemical abnormalities suggesting […]
Clinical spectrum and pleiotropic nature of CDH1 germline mutations
The human CDH1 gene codes for E-cadherin, a cell-cell adhesion molecule that is essential for embryonic development and organization of adult epithelial tissues. Carriers of a CDH1 germline mutation have a lifetime risk of diffuse gastric cancer (DGC) of up to 80% and women have also a probability of 42% of developing lobular breast cancer […]
Longitudinal evaluation of SMN levels as biomarker for Spinal Muscular Atrophy Molecular: results of a phase-IIb double-blind study of salbutamol
Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder, due to the loss of the SMN1 gene. We have performed a 1-year placebo-controlled study with salbutamol, a compound commonly used for asthma, in SMA adult patients. Objectives of the study were the usefulness of SMN dosage in blood, and the safety of oral salbutamol. Beside […]
MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, Craniofacial and genital features (COFG syndrome)
This article delineates a novel syndrome, which was named COFG syndrome with respect to the developmental defects observed: brain malformations, especially affecting the cerebellum, developmental delay and intellectual disability, developmental defects of the external genitals resulting in absence of the scrotum in boys and absence of the labia majora in girls, eye anomalies and distinctive […]
Does multilocus inherited neoplasia alleles syndrome have severe clinical expression?
We describe the analysis of 1023 unrelated patients with suspicion of hereditary cancer using an in house-designed 135 gene panel. We identified thirteen (1.37%) patients with two pathogenic mutations in dominant cancer-predisposing genes, representing 5.7% (13/226) of patients with pathogenic mutations. This phenomenon is known as Multilocus Inherited Neoplasia Alleles Syndrome (MINAS) and has been […]
MYCN de novo gain-of-function mutation in a patient with a novel megalencephaly syndrome
We identified a heterozygous missense mutation (c.173C>T; p.Thr58Met) in the MYCN gene in an individual with megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly and neuroblastoma. The mutation occurred at Thr58 phosphorylation site essential for ubiquitination and subsequent MYCN degradation. In vitro and in vivo analysis suggested that this mutation stabilized and accumulated MYCN protein […]
Biallelic mutations in USP45, encoding a deubiquitinating enzyme, are associated with Leber congenital amaurosis
Leber congenital amaurosis (LCA) is the earliest and most severe form of inherited retinal dystrophies, accounting for approximately 20% of children attending schools for the blind. Currently, the genetic defects could be identified in about 60% of families with LCA in one of the 25 causative genes, including RPE65 in which a new gene therapy […]