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 […]
Latest articles
Cancer immunotherapy: challenges and clinical applications (Contributed by An-Liang Xia and Xiao-Jie Lu)
Nowadays, cancer immunotherapy has emerged as one of the standard treatment modalities against cancer. It has made great progress in two areas: immune checkpoint inhibitors and chimeric antigen receptor (CAR)-modified T cells. Immune checkpoint inhibitors, including anti-PD-1 and anti-CTLA-4 mAbs, are applied to eliminate the ‘brakes’ on the immune system that can impede immune cells […]
Practice evaluation of biobank ethics and governance: current needs and future perspectives (Contributed by Holger Langhof)
Biobank research faces many ethical challenges, such as obtaining valid consent from donors or dealing with incidental findings. Ethicists have long been engaged in the development of ethical standards to meet these challenges. However, it is often unclear if and how these standards are applied in practice. In our study we reviewed the scientific literature […]
Novel homozygous CFAP69 mutations in humans and mice cause severe asthenoteratospermia with multiple morphological abnormalities of the sperm flagella (Contributed by Dr. Xiaojin He)
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 […]
Constitutional mismatch repair deficiency as a differential diagnosis of neurofibromatosis type 1: consensus guidelines for testing a child without malignancy (Contributed by Manon Suerink and Dr. Katharina Wimmer)
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 (Contributed by Dr. Vincenzo Lupo)
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 (Contributed by Dr. Camille Tlemsani)
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 (Contributed by Crawford et al.)
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 (Contributed by Dr. Saquib Lakhani)
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 (Contributed by Dr. Hildur Helgadottir)
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 […]