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 […]
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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, […]
Mapping of breakpoints in balanced chromosomal translocations by shallow whole genome sequencing points to EFNA5, BAHD1 and PPP2R5E as novel candidates for genes causing human Mendelian disorders
Mapping breakpoints in patients with de novo balanced chromosomal translocation (BCTs) offers a unique possibility for identification of new genes causing human monogenic disorders, even when only single patients are studied. Historically, solving the exact structure of BCTs was laborious, but with the emergence of next generation sequencing (NGS) it became possible to rapidly map […]
Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome of unknown etiology
Maternal uniparental disomy of chromosome 16 (UPD(16)mat) is defined as the presence of two homologous chromosomes 16 inherited from only the mother. Silver-Russell syndrome (SRS) is characterized by growth failure and dysmorphic features, and molecular etiology is unknown in some of the SRS patients. The prevalence of UPD(16)mat in etiology-unknown SRS patients and phenotypic differences […]