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 […]
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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 […]
Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning
The article found some significantly mutated genes in CC using NGS technology and predicted that 55.9% of CC patients might potentially benefit from targeted drugs. And HPV integrations occurred in 97.8% of the CCs, 70.5% of the CINs and 42.8% normal cervical samples with HPV infection. Integrations of high-risk HPV strains in CCs, including HPV16, […]
Meiotic chromatid recombination and segregation assessed with human single cell genome sequencing data
During meiosis of human oocytes, parental homologous chromosomes will occur DNA double-strand breaks (DSBs) based recombination which is a reciprocal genetic information exchange. In our study, we found a part population of oocytes exist a genome conversion phenomenon in which one chromosome could give up a large part of its DNA and repair it with […]
Screening of BRCA1/2 deep intronic regions by targeted gene sequencing identifies the first germline BRCA1 variant causing pseudoexon activation in a patient with breast/ovarian cancer
Pathogenic germline variants in BRCA1 and BRCA2 genes confer increased breast/ovarian cancer (BC/OC) risks. The identification of deleterious BRCA1/2 genetic variants in BC/OC families guides the enrollment of carriers in medical surveillance and cancer prevention programs and informs treatment decisions by more precisely targeted cancer therapies. BRCA1/2 genetic analysis commonly includes only coding regions. However, […]