The article found two novel CFAP69 pathogenic variants in a cohort of 35 asthenoteratospermia with short, coiled and irregular flagella. The authors also generated Cfap69 knockout mouse and found the similar sperm flagella defects in mice. This article provide a strong evidence of the CFAP69 variants and asthenoteratospermia. These findings indicate that asthenoteratospermia with special […]
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Constitutional mismatch repair deficiency as a differential diagnosis of neurofibromatosis type 1: consensus guidelines for testing a child without malignancy
Constitutional mismatch repair deficiency (CMMRD) is a very rare genetic condition conferring an extraordinarily high risk for development of cancer already during childhood and young adulthood. Patients with this cancer syndrome frequently have multiple café-au-lait spots and other signs that are indicative of a different, much more common condition, which is neurofibromatosis type 1 (NF1) […]
Characterising the phenotype and mode of inheritance of patients with inherited peripheral neuropathies carrying MME mutations
Mutations in MME gene has previously been reported to cause autosomal recessive (AR) Charcot-Marie-Tooth disease type 2 (CMT2) and also to be associated with late-onset autosomal dominant (AD) polyneuropathies. In our cohort, we found that MME mutations co-segregated with the disease following an exclusive AR pattern of inheritance. Moreover, patients carrying heterozygous mutations in our […]
Chemoresistant pleomorphic rhabdomyosarcoma: whole exome sequencing reveals underlying cancer predisposition and therapeutic options
We report the case of a patient with a metastatic chemoresistant sarcoma. Considering the few therapeutic options, we performed an extensive sequencing of the tumor and leucocytes DNA. We identified a constitutional mutation in the MLH1 gene which was not expected considering the family history. Because of this mutation affecting genome stability, we expected that […]
Medical consequences of pathogenic CNVs in adults: Analysis of the UK Biobank
Pathogenic copy number variants (CNVs) are deletions or duplications of large stretches of chromosomes, that have been shown to cause developmental delay, autism spectrum disorders and schizophrenia. The UK Biobank, with half a million well-phenotyped participants, provides an unprecedented opportunity to examine whether these CNVs increase risk to develop other medical disorders. We analysed the […]
De novo pathogenic variants in neuronal differentiation factor 2 (NEUROD2) cause a form of early infantile epileptic encephalopathy
Early infantile epileptic encephalopathies (EIEEs) are severe disorders characterized by drug-resistant seizures and developmental delay. More than 100 genes have been associated with EIEEs, with genetic and phenotypic heterogeneity. Two unrelated patients with EIEE presented with de novo mutations in Neuronal Differentiation Factor 2 (NEUROD2), which had not been previously reported in any human disease. […]
Efficacy of novel immunotherapy regimens in patients with metastatic melanoma with germline CDKN2A mutations
Inherited mutation in the tumor suppressor gene CDKN2A is one of the strongest known risk factors for melanoma of the skin. Moreover, carriers have been found to have poor melanoma-specific survival. In this study, responses to novel immunotherapy agents (PD-1 and CTLA-4 inhibitors) in CDKN2A mutation carriers with metastatic melanoma were evaluated. Eleven of nineteen affected carriers (58%) responded […]
Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study
Type 1 diabetes, which is the most common metabolic disease in children and adolescents, begins with a pre-clinical phase which is defined by the presence of islet autoantibodies. This pre-clinical phase is variable in duration with onset of clinical diabetes occurring months to decades after the appearance of islet autoantibodies. In this study, we found […]
Investigation of clinically relevant germline variants detected by next-generation sequencing in patients with childhood cancer: a review of the literature
Genomic technologies have enabled the sequencing of childhood cancer patients to investigate genetic predisposition. This review compares 6 studies of selected cohorts of childhood cancer patients reporting clinically relevant pathogenic germline variants in a broad spectrum of genes associated with susceptibility to both adult and paediatric cancers. We identified differences in the reported incidence of […]
Mosaicism and incomplete penetrance of PCDH19 mutations
Point mutations or rearrangements involving the PCDH19 gene located on Xq22.1 cause epilepsy and mental retardation mainly in females. However, affected males with mosaic PCDH19 mutations have also been reported. It is hypothesized that cellular interference mechanism is the main pathogenic mechanism. In our 42 PCDH19-related epilepsy families, five mosaic individuals, four males and one female, […]