“Methylglutaconic aciduria, Deafness, Encephalopathy, Leigh-like” syndrome (MEGDEL syndrome) is a genetic disease caused by mutations in a gene named SERAC1, which is involved in the metabolism of specific lipids, so-called phosphatidylglycerols. MEGDEL syndrome typically presents with progressive deafness, motor symptoms (i. e. dystonia) and additional features (e. g. neonatal sepsis and liver failure) with onset […]
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Hypothesis: lobe A (COG1–4)-CDG causes a more severe phenotype than lobe B (COG5–8)-CDG
Some cellular components may be more equal than others. In this study we used the frequency gap – underreporting of a certain phenomenon – to determine the relative importance of both A and B lobes for the functioning of a protein complex called “the COG complex”. Two observations suggest that the consequences of lobe A […]
CTCF deletion syndrome: clinical features and epigenetic delineation
CTCF has multiple function in epigenetics including X-chromosome inactivation, genomic imprinting and genome organization. Mutations in CTCF are known to cause intellectual disability, however mechanism underlying the disease remains unknown. In this study, we reported two patients with a deletion including CTCF and proposed CTCF deletion syndrome because they showed distinct clinical characteristics icluding intellectual […]
Genetic Severity Score predicts clinical phenotype in NF2
Individuals affected with Neurofibromatosis type 2 (NF2) typically develop multiple brain and spine tumours, and often lose hearing in young adulthood. The disease course can vary amongst patients and their severity is linked to genetic variations. The NF2 genetic severity score presented here, groups patients using genetic test results. The score separated patients according to […]
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 […]
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 […]
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 […]
Mutations in SCAPER cause autosomal recessive retinitis pigmentosa with intellectual disability
Retinitis pigmentosa (RP) is a hereditary eye disease marked by progressive degeneration of the retina – the part of the eye that is home to the photosensitive cells. RP can occur by itself or in combination with other impairments. The latter cases are known as syndromic RP. We identified mutations in a gene named SCAPER […]
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 […]
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 […]