Psychosocial effects of whole-body MRI screening in adult high-risk pathogenic TP53 mutation carriers: a case-controlled study (SIGNIFY)

People who are born with a pathogenic (disease-causing) variant in the TP53 gene have a very high lifetime risk of developing cancer – almost 100% for women and 75% for men.  The SIGNIFY study, which reported last year, found that whole body Magnetic Resonance Imaging (WB-MRI) in people known to carry a pathogenic variant in […]

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Cornelia de Lange syndrome: from molecular diagnosis to therapeutic approach

Cornelia de Lange syndrome (CdLS) is a rare disease characterized by facial dysmorphism, pre- and postnatal growth retardation, cognitive impairment, gastrointestinal malformations, congenital heart abnormalities and limb defects. CdLS results from nucleotide changes in genes belonging to the cohesin pathway, involved in many biological processes important for cell life. CdLS cells show several dysregulated pathways, […]

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Homozygous mutations in REC114 cause female infertility characterised by multiple pronuclei formation and early embryonic arrest

Abnormal pronuclear formation during fertilization and subsequent early embryonic arrest result in female infertility. In recent years, a few genes have been identified that are involved in female infertility caused by abnormalities in oocyte development, fertilization, and embryonic development. However, the genetic factors responsible for multiple pronuclei formation during fertilization and early embryonic arrest remain […]

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Intronic SMCHD1 variants in FSHD: testing the potential for CRISPR-Cas9 genome editing

Facioscapulohumeral muscular dystrophy (FSHD) type 2 is a hereditary muscle disease which can be caused by mutations in the SMCHD1 gene. While most SMCHD1 mutations are found in the DNA coding for the protein (exon), we here report FSHD-causing mutations in non-coding regions of the SMCHD1 gene (introns). This shows that these regions should be […]

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Gastric polyposis and desmoid tumours as a new familial adenomatous polyposis clinical variant associated with APC mutation at the extreme 3′-end

Germline mutations of the APC gene, which encodes a multidomain protein of 2843 amino acid residues, cause familial adenomatous polyposis (FAP). Truncating mutations in APC extreme 3’-end are rare and have not been clearly associated with a specific phenotype. Here we studied 101 clinically characterized patients harboring truncating mutations in APC extreme 3’-end in order […]

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Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia

A patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy was sequenced by whole-exome sequencing, revealing a homozygous variant in KCNA1. This newly identified variant is the first to be reported to act in a recessive mode of inheritance in this gene. Functional analysis showed that mutant protein alone failed to produce functional channels, while […]

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Increasing knowledge in IGF1R defects: lessons from 35 new patients

The IGF1R is a keystone of fetal growth regulation by mediating the effects of IGF-I and IGF-II. We detected 21 IGF1R defects in patients with fetal growth restriction, including 8 heterozygous CNVs and 10 heterozygous, 1 homozygous, and 1 compound-heterozygous SNVs. We validated a scoring system based on fetal and post-natal growth retardation, microcephaly and […]

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Paediatric systemic lupus erythematosus as a manifestation of constitutional mismatch repair deficiency

Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessive cancer predisposition syndrome, causing café au lait macules, brain malformations and and multiple tumors, mostly leukemia/ lymphoma, brain, and gastrointestinal cancer in the first two decades. Early recognition of CMMRD may allow tailored surveillance and genetic counseling, also for heterozygote carriers who have Lynch syndrome. We […]

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Biallelic Mutations in CFAP65 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella in Humans and Mice

Male infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) is a genetically heterogeneous disorder. Previous studies revealed several MMAF-associated genes, which account for approximately 60% of human MMAF cases. The pathogenic mechanisms of MMAF remain to be illuminated. In this study, we identified biallelic mutations of the CFAP65 gene in the MMAF […]

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