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 […]
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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 […]
Combined Mineralocorticoid and Glucocorticoid deficiency is caused by a novel founder Nicotinamide Nucleotide Transhydrogenase mutation that alters mitochondrial morphology and increases oxidative stress
The novel and ancestral NNT mutation, p.G200S, which was identified in two unrelated consanguineous families, expands the glucocorticoid deficiency phenotype of NNT mutations to include also mineralocorticoid deficiency; and thus present in early life with severe salt loss, low blood pressure and hypoglycemia. We provide the first patient-based evidence that NNT mutations induce oxidative stress […]
Breakpoint mapping by whole genome sequencing identifies PTH2R gene disruption in a patient with midline craniosynostosis and a de novo balanced chromosomal rearrangement
Craniosynostosis (CRS) is premature closure of cranial sutures, which is caused by either a gene mutation or environmental factors or both. Herein we found a gene mutation causing midline non-syndromic craniosynostosis in a 15-month-old boy. Conventional chromosome study revealed a complex paracentric inversion involving 2q14.3 and 2q34, and multicolor banding refined breakpoints to 2q14 and […]