Categoría: Open access
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Long-term efficacy of migalastat in females with Fabry disease
Background Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to GLA variants. Females with Fabry disease often experience diagnostic delays and an underappreciated disease burd…
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Refined genotype-phenotype correlations in neurofibromatosis type 1 patients with NF1 point variants
Background Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders. NF1 is caused by dominant loss-of-function pathogenic variants (PVs) of the tumour-suppressor gene NF1, which encodes neurofibromin, a negative regulator of rat s…
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APC I1307K and clinical management: insights from UK Biobank association analysis of colorectal and other cancer risks in Ashkenazi and non-Ashkenazi whites
Background APC c.3920T>A; p.Ile1307Lys (I1307K), prevalent in individuals of Ashkenazi Jewish (AJ) origin, has been associated with a modestly increased colorectal cancer (CRC) risk. Clinical recommendations for I1307K heterozygotes vary across c…
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Reproductive carrier screening for genetic disorders: position statement of the Canadian College of Medical Geneticists
Purpose and scope The aim of this position statement is to provide recommendations aimed at Canadian reproductive care clinicians and genetics professionals regarding the use of reproductive carrier screening for autosomal recessive and X-linked reces…
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Development of a functional assay for the characterisation of SMAD4 variants from the French haemorrhagic hereditary telangiectasia cohort
Background Hereditary haemorrhagic telangiectasia (HHT) and juvenile polyposis syndrome (JPS) can be caused by SMAD4 pathogenic variants. SMAD4 is a common transcription factor of the BMP/TGFβ signalling pathway. In this study, we developed a cel…
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PURA protein mislocalisation in the nucleus: mechanistic basis for transcriptional dysregulation and DNA unwinding deficits in a model of the p.L148Wfs*77 PURA variant
Background Heterozygous PURA (Purine-rich element-binding protein A) variants cause PURA syndrome, a neurodevelopmental disorder characterised by hypotonia, seizures and intellectual disability. Previous studies have focused on the effect of the PURA …
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Genetic and embryonic transcriptome analyses reveal the molecular and developmental basis of Mayer-Rokitansky-Küster-Hauser syndrome
Background Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterised by aplasia of the uterus, cervix and upper part of the vagina. The genetic aetiology remains incompletely understood. Methods We performed gene-level and gene set-lev…
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No association of Alzheimer disease with the joint effect of HFE and TF in the mid-western Amish
Variants in iron metabolism genes have been implicated in Alzheimer Disease (AD) pathogenesis.1 2 Previous studies suggested that the joint effect of haemochromatosis (HFE) C282Y (rs1800562) and transferrin (TF) C2 (P589S, rs1049296) variants increase…
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Recontact and follow-up for individuals with germline pathogenic variants in hereditary breast and ovarian cancer susceptibility genes: a UK Cancer Genetics Group consensus meeting
Background Routine genetic testing for germline pathogenic variants (GPVs) in cancer susceptibility genes (CSGs) in individuals with suspected hereditary cancer risk, and subsequent cascade testing in close relatives, has led to a significantly increa…
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Health-related quality of life in patients with mitochondrial disease and their carers
Background Mitochondrial diseases are a group of rare, chronic disorders with a significant disease burden; however, there is limited knowledge about their effects on the health-related quality of life (HRQoL) of patients and their carers. This study …