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 […]
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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 […]
Hereditary lobular breast cancer with an emphasis on E-cadherin genetic defect
Hereditary lobular breast cancer is an inherited syndrome that is associated with the CDH1 germline mutations. The CDH1 gene plays a crucial role in the correct function of human cells. Loss of the encoded protein, so called E-cadherin, represents a dramatic event; in human epithelial cancers, as diffuse gastric and lobular breast tumors, this loss […]
Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment
CEACAM16 is an adhesion protein that plays a critical role in ensuring proper auditory function. Defects in this protein have been linked to dominant hearing loss through a dominant-negative mechanism. Here we report that novel splice-altering variants in CEACAM16 gene are associated with autosomal recessive nonsyndromic hearing loss. Our findings broaden the pathogenic mechanisms of […]
From gestalt to gene: early predictive dysmorphic features of PMM2-CDG
Phosphomannomutase-2 deficiency (PMM2-CDG) is the most frequent congenital disorder of glycosylation and it is associated with a recognizable facial pattern. There are no phenotype-genotype correlations neither early severity predictors. We evaluate dysmorphic features and propose a classification dividing them into major and minor with diagnostic implications. We elaborated a severity dysmorphology categorization with proven predictive […]