Etiqueta: #JMedGenet
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Identification of biallelic loss-of-function PREP variants in three individuals with syndromic intellectual disability
Background Neurodevelopmental disorders are one of the most prevalent reasons for genetic testing in childhood. Despite the identification of over 1950 associated genes, many proposed candidate genes lack convincing gene-disease validity. The gene PRE…
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Interpreting TP53 variants: somatic mosaicism and ERCC6L2-driven clonal evolution
We present two illustrative cases highlighting diagnostic, surveillance and management complexities of TP53 pathogenic variants (PVs). Case 1 describes a 24-year-old female with early-onset breast cancer and a somatic mosaic TP53 PV with a variant all…
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PRS-BC313 integration for tailored breast cancer prevention in female patients and their healthy relatives
Precise breast cancer risk assessment (BCR) is essential for personalised prevention in women with a family history of hereditary breast and ovarian cancer (HBOC). The CanRisk model integrates monogenic variants with reproductive, lifestyle and famili…
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Review of estimates of birth incidence and population prevalence over time and between countries of the rare neurodevelopmental condition Prader-Willi syndrome
Epidemiological data such as birth incidence or population prevalence for rare conditions is difficult to obtain because of the large sample size required in order to obtain a valid estimate (ie based on a reasonable number of cases) and the difficult…
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Identification of a novel intergenic EPCAM-MSH2 deletion causing EPCAM-associated Lynch syndrome by long-read nanopore sequencing
Epithelial cell adhesion molecule (EPCAM)-associated Lynch syndrome arises from deletions at the 3′-end of EPCAM that disrupt transcriptional termination, generate read-through transcripts and cause epigenetic silencing of MSH2 in EPCAM-expressing tis…
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Biallelic pathogenic variants in FLNB are associated with paediatric steroid-resistant nephrotic syndrome via podocyte cytoskeletal dysfunction
Background Steroid-resistant nephrotic syndrome (SRNS) is a severe paediatric kidney disease and a leading cause of end-stage kidney disease in children, with a high genetic contribution. While over 80 monogenic causes of SRNS have been identified, a …
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Decreasing diffuse gastric cancer risk in individuals with germline CDH1 pathogenic variants. What about prophylactic total gastrectomy?
Background We read with interest the recent original paper by Benusiglio et al.1 The authors reported a series of 20 individuals at high risk for diffuse gastric cancer (DGC) with a documented germline CDH1 pathogenic variant. These individuals refuse…
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Location matters: topography of germline CEBPA variants predicts variable outcomes in familial acute myeloid leukaemia–a rare disease perspective
Background Familial acute myeloid leukaemia (AML) with germline CEBPA (CCAAT/enhancer-binding protein alpha) variants is a distinct hereditary entity, yet clinically meaningful genotype–phenotype correlations remain incompletely defined. Method…
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Identification of Lynch syndrome among people newly diagnosed with endometrial cancer: a prospective audit
Background Since 2020, the UK National Institute for Health and Care Excellence (NICE) recommends screening for Lynch syndrome in all people newly diagnosed with endometrial cancer. Screening involves tumour testing for loss of the mismatch repair (MM…
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Phenotypic description of a large French series of individuals with Potocki-Lupski syndrome
Background Potocki-Lupski syndrome (PTLS) is a rare genetic disorder, with an estimated prevalence of 1:25 000. Detection of a duplication at position 17p11.2 comprising the RAI1 gene establishes the diagnosis. Deletion of this same region is responsi…