Up to 70% of patients with pheochromocytoma or paraganglioma (PPGL) harbor a somatic or germline mutation in one of the 22 genes described so far as related to the disease. However, patients with apparently sporadic PPGL tend to be excluded from genetic testing. This study should bring to an end years of controversy and debate, […]
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WAC loss-of-function mutations cause a recognisable syndrome characterised by dysmorphic features, developmental delay and hypotonia and recapitulate 10p11.23 microdeletion syndrome
Mutations in the WAC gene have been recently reported in large screening cohorts of patients with intellectual disability or autism. We used whole exome sequencing to evaluate 6 patients with developmental delay, hypotonia, behavioral problems, constipation/feeding difficulties and common dysmorphic features including broad/prominent forehead, synophrys and/or bushy eyebrows, depressed nasal bridge and bulbous nasal tip. […]
Old gene, new phenotype: mutations in heparan sulfate synthesis enzyme, EXT2 leads to seizure and developmental disorder, no exostoses
Heparan sulfate proteoglycans are essential for human development. Many genes are involved in producing heparan sulfate and when these genes are mutated, they can lead to early-onset developmental disorders affecting multiple body systems. Our group identified a family with a disease designated as seizures-scoliosis-macrocephaly syndrome, which is characterized by seizures, intellectual disability, scoliosis, and prominent […]
Charcot–Marie–Tooth diseases: an update and some new proposals for the classification
Charcot-Marie-Tooth (CMT) disease is the most frequent form of inherited neuropathy. To date, more than 60 genes have been implicated in this heterogeneous group of neuropathies, and the recent advances in genetic technologies are promising. In this review, we discuss the diagnostic approaches and the underlying complex molecular processes. We also suggest a modification of […]
Mutations in COQ4, an Essential Component of Coenzyme Q Biosynthesis, Cause Lethal Neonatal Mitochondrial Encephalomyopathy
Coenzyme Q10 is an essential cofactor for mitochondrial function and other biochemical pathways. Mutations in genes involved in CoQ10 biosynthesis cause primary CoQ10 deficiency syndromes that can be treated with oral ubiquinone. We used exome sequencing to evaluate 6 patients with clinical findings suggestive of a mitochondrial disorder. All patients were female and presented on […]
Whole exome sequencing identifies LRP1 as a pathogenic gene in autosomal recessive keratosis pilaris atrophicans
Keratosis pilaris atrophicans (KPA) is a group of related skin disorders characterized by inflammatory keratotic skin-papules and hair loss on the scalp, eyebrows and eye-lashes. Facial scarring is a complication. A consanguineous family with four members affected by KPA was subject to extensive genetic investigation. The analysis revealed that affected individuals had inherited a unique […]
A CASQ1 founder mutation in 3 Italian families with protein aggregate myopathy and hyperCKaemia
Chronic elevation of serum creatine kinase (CK) is a common manifestation of neuromuscular disorders and may precede disease clinical expression, or remain asymptomatic. In 3 Italian families having high CK, mild myopathy, and calsequestrin-positive inclusions in muscle fibers, exome and Sanger sequencing and linkage analysis revealed a founder mutation in the CASQ1 gene. Immunocytochemistry, electron […]
Continued lessons from the INS gene: an intronic mutation causing diabetes through a novel mechanism
Neonatal diabetes (diagnosed under 6 months of age) is usually caused by a disruption (mutation) in one of over twenty diabetes-related genes. One of the most common causes of neonatal diabetes is mutations in the insulin gene that result in production of a misshaped insulin protein that leads to death of the insulin producing beta […]
Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4–dihydroxybensoic acid
Coenzyme Q (CoQ10) is an essential mitochondrial electron carrier, redox cofactor and a potent antioxidant in the majority of cellular membranes. A range of metabolic diseases, as well as the ageing process and prolonged statin treatments have been associated with CoQ10 deficiency. Here the first case of a primary CoQ10 defect due to a mutation […]
Exploring genotype-phenotype relationships in Bardet-Biedl syndrome families
Bardet Biedl syndrome (BBS) is a recessive rare disorder included in the ciliopathies disease family. The patient´s phenotype is very important in order to go deeper into the physiopathology of the disease. The clinical description of the patients could give us some clues about the pathways that are involved in the disease. Besides, the more […]