Etiqueta: #JMedGenet
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Intragenic loss-of-function variants in transcription factors MAZ, FOXP1 and SIN3B in colobomatous microphthalmia
Despite the identification of many genes involved in developmental eye phenotypes, a large percentage of families lack genetic diagnoses, suggesting novel mechanisms remain to be discovered. Large deletions of 16p11.2, 3p14 or 19p13.11 regions involvi…
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Association for Clinical Genomic Science (ACGS) guidelines for the classification of oncogenicity of somatic variants in cancer: recommendations by the UK somatic variant interpretation group (SVIG-UK)
Comprehensive genomic testing in routine cancer care pathways has created the need to interpret the consequences of somatic (acquired) genomic variants beyond the currently well-characterised driver variants in cancer gene hotspots. While several guid…
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ACTH-secreting atypical carcinoid lung tumour expanding the Lynch syndrome spectrum
Neuroendocrine tumours (NETs) are increasingly associated with Lynch syndrome (LS). In this autosomal dominant cancer predisposition syndrome, a somatic mutation in addition to a germline pathogenic variant is required for tumour development. We descr…
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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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Mixed functional consequences of the N651D GRIA3 variant: a case of early-onset developmental and epileptic encephalopathy with parkinsonism
Rare variants in GRIA3, the gene encoding the GluA3 subunit of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs), are associated with defects in early brain development. Disease-causing variants are generally …
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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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Further evidence of RNU4ATAC variants causing Joubert syndrome with skeletal involvement
RNU4ATAC is a non-coding gene involved in the minor spliceosome, and is mutated in a spectrum of syndromic skeletal disorders with recessive inheritance. Recently, biallelic RNU4ATAC pathogenic variants were detected in five patients presenting a co…
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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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Inefficiencies in precision medicine: can genetic counsellors (GC) be the solution? The experience from the first GC-led cancer genetics service in Asia
Purpose The utility of genetic testing (GT) to guide cancer treatment, risk management and prevention has driven the demand for cancer genetic services. The global shortage of genetic counsellors (GCs) has led to the mainstreaming model. We evaluate t…
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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…