Fabry disease: characterisation of the plasma proteome pre- and post-enzyme replacement therapy

Fabry disease (FD) is characterized by the progressive accumulation of globotriaosylceramide (Gb3). Enzyme replacement therapy (ERT) clears this accumulation. We analyzed plasma proteome profiles before and after ERT to characterize its molecular pathology. After ERT, the levels of proteins involved in inflammation, oxidative and ischemic injury, or complement activation were reduced significantly. In particular, we found out that inactivated complement C3b (iC3b) was significantly […]

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Autosomal recessive chondrodysplasia with severe short stature caused by a biallelic COL10A1 variant

Individuals carrying single mutated copies of Collagen 10 alpha-1, (COL10A1) suffer from Metaphyseal chondrodysplasia, Schmid type, (MCDS), involving mild to moderate short stature and skeletal deformities of the limbs. We describe individuals with two mutated copies of COL10A1, exhibiting extreme short stature and severe lower limb deformities. However, individuals with single mutated copies had below […]

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Their loss is our gain: regressive evolution in vertebrates provides genomic models for uncovering human disease loci

What can an armadillo tell us about blindness and an anteater about dental disorders? Many animals have evolved traits that are similar to human genetic diseases, although for these animals the traits are adaptive, not disease-causing. Intriguingly, when animals possess these disease-mimicking traits, they frequently have disabling mutations in the same genes underlying the human […]

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Heterogeneous clinical spectrum of DNAJC12-deficient hyperphenylalaninemia: from attention deficit to severe dystonia and intellectual disability

Hyperphenylalaninemia is one of the most common inherited metabolic diseases diagnosed in the newborn screening and until now follow-up investigation included differential diagnosis of phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiency. With the description of patients with biallelic variants in co-chaperone DNAJC12 (van Spronsen et al 2017), the paradigm of hyperphenylalaninemia needs reconsideration. DNAJC12-deficient patients may […]

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A common SLC26A4-linked haplotype underlying non-syndromic hearing loss with enlargement of the vestibular aqueduct

Two mutated copies of the SLC26A4 gene are associated with Pendred syndrome, comprised of bilateral hearing loss with enlargement of the vestibular aqueduct (EVA) and thyroid goiter.  Other EVA patients have a normal thyroid gland and only one mutated copy of SLC26A4.  Our study identified the same combination, or haplotype, of noncoding sequence variants upstream […]

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Increased Breast Cancer Risk in MSH2 Carriers from a Large Canadian Familial Cancer Registry

Lynch Syndrome is an inherited condition involving several well-characterized mutations; MLH1, MSH2, MSH6, and PMS2. Affected families are counselled on their increased risk of numerous malignant diagnoses including colorectal cancer and endometrial cancer, as well as central nervous system malignancies and several other gastrointestinal and genitourinary cancers. Management of Lynch Syndrome includes prevention and surveillance, […]

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Segregation of mitochondrial DNA mutations in the human placenta: implication for prenatal diagnosis of mtDNA disorders

Mitochondrial cytopathies are genetic diseases, some of which result from mutations affecting part of the multiple DNA molecules located within mitochondria (mtDNA). Coexistence of mutant and wild-type mtDNA molecules is called “heteroplasmy” and defines a “mutant load”. Disease symptoms occur when the mutant load surpasses a tissue-specific threshold. Owing to the absence of therapy and […]

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A germline deletion of 9p21.3 presenting as familial melanoma, astrocytoma and breast cancer: clinical and genetic counselling challenges

Very few families with 9p21.3 deletion have been described. These families are at risk of developing melanoma and nerve sheath tumors.  We report a family with several members affected by melanoma, astrocytoma, neurofibromas, and breast cancer. They have a 9p21.3 deletion containing 9 genes. While mutations within individual genes are associated with distinct hereditary cancer […]

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Identification of the first dominant mutation of LAMA5 gene causing a complex multisystem syndrome due to dysfunction of the extracellular matrix

Laminin alpha 5 gene (LAMA5) plays a master role in the extracellular matrix in all mammalian tissues; mice defective of LAMA5 do not overcome embryonic life. In this paper a previously unknown autosomal dominant clinico-pathological syndrome is described which segregates with the mutation c.9418G>A (p.V3140M) of LAMA5 in an informative Italian family.  The results of […]

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