Etiqueta: #JMedGenet
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Comprehensive genotype-phenotype correlation analysis in 11 509 neonates carrying common deafness-associated pathogenic variants
Background This study aimed to analyse the distribution and genotype-phenotype correlations of pathogenic variants among 11 509 newborns carrying at least one common deafness-associated variant. Methods A genotype distribution analysis was performed …
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Comparison of clinical characteristics between patients with single mutation and co-mutation in hereditary renal cancer: a retrospective analysis of 115 patients with von Hippel-Lindau syndrome
Purpose von Hippel-Lindau (VHL) syndrome-related renal cell carcinoma (RCC) is the most prevalent hereditary RCC and exhibits clinical heterogeneity, complicating patient management. While VHL gene inactivation is the primary driver, the impact of co-…
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Diagnostic genetic testing indications and findings in type II, IX and XI collagenopathies
Background Type II, IX and XI collagenopathies encompass Stickler syndrome and a spectrum of related connective tissue disorders with diverse and overlapping phenotypes. This study evaluated outcomes of commercial gene panels to understand how genetic…
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Diagnosis complexity of dentinogenesis imperfecta involving DSPP genetic variants
Background Variants in the dentin sialophosphoprotein (DSPP) gene are associated with dentin dysplasia type II (DD-II; OMIM # 125420) and dentinogenesis imperfecta (DI) types II (OMIM # 125490) and III (OMIM # 125500). DSPP encodes a precursor protein…
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Colonoscopy surveillance in Lynch syndrome: what it prevents and what it does not
Lynch syndrome (LS), synonymous with hereditary non-polyposis colorectal cancer (HNPCC), is caused by germline pathogenic variants in MLH1, MSH2, MSH6 or PMS2, which confer an elevated lifetime risk of colorectal cancer (CRC). Since the early 2000s, c…
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MGRN1 is linked to recessive heart and laterality defects: the first genotype-phenotype report in humans
Recurrent idiopathic severe fetal structural anomalies present major challenges for reproductive decision-making and genetic counselling. A non-consanguineous healthy Estonian couple had experienced two electively terminated pregnancies at 12–13…
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Comprehensive evidence for the pathogenicity of the BRCA2 c.7847C>T (p.Ser2616Phe) variant specific to the Japanese population
Background The BRCA2 c.7847C>T (p.Ser2616Phe) variant is specific to the Japanese population and has long remained a variant of uncertain significance. Because BRCA1/2 genetic testing serves as a companion diagnostic for poly (ADP-ribose) polymeras…
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End of a diagnostic odyssey: the added value of multi-tissue analysis in the identification of mosaicism in tumour predisposition syndromes
Mosaicism refers to the presence of multiple cell clones with distinct genotypes arising from a single zygote. The phenotype of mosaic individuals depends on the extent of mosaicism, ranging from localised to almost generalised. We report three diagno…
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CDK4 and CDK6 variants in patients with primary microcephaly lead to cell cycle defects and mitochondria-induced apoptosis
Background The disruption of neural progenitor proliferation is a key mechanism underlying primary microcephaly, yet how cell cycle arrest leads to progenitor loss remains only partially understood. Cyclin-dependent kinases, CDK4 and CDK6, are central…
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Unmasking NF1 mosaicism: optical genome mapping identifies a novel t(15;17) translocation in melanocytes
Mosaic neurofibromatosis type 1 (NF1) poses a significant diagnostic challenge due to low-level mosaicism and the confinement of pathogenic variants to neuroectodermal lineages, frequently resulting in false-negative findings when testing is limited t…