Categoría: Open access
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Diagnosis complexity of dentinogenesis imperfecta involving DSPP genetic variants
BackgroundVariants 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 c…
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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 diagnos…
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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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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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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 diagnos…
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Inherited variants in autosomal dominant disease genes are a significant cause of fetal structural anomalies
Background Monogenic disorders are a major cause of fetal structural anomalies. Most genetic diagnoses involve de novo, biallelic or X linked variants; however, inherited variants in autosomal dominant disease genes have been detected across multiple …
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Later age of natural menopause among women with the pathogenic CHEK2 c.1100delC variant: a validation study
Background The average age of natural menopause (ANM) for European women is 50–52 years. Reproductive risk and lifestyle factors have been found to be associated with ANM. Furthermore, a genome-wide association study found that women with a CHEK…
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Frequency of familial hypercholesterolaemia-causing genetic variants in the 100 000 Genomes Project cohort: whole genome sequencing analyses of 77 260 participants
Background Heterozygous Familial Hypercholesterolaemia (HeFH) is caused by pathogenic variants in LDLR, APOB, APOE or PCSK9, leading to elevated low-density lipoprotein-cholesterol and increased cardiovascular risk. In the UK, HeFH affects ~1 in 288 i…
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MITF (p.E318K) and renal cell carcinoma: current evidence does not support an effect
The microphthalmia-associated transcription factor (MITF) is a key regulator of melanocyte development, function and survival. The p.E318K variant affects SUMOylation at K316 and has been shown to alter MITF’s genome occupancy, potentially influ…
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How do clinician and parent-reported data differ? An analysis of similarity and difference in the datasets from a cross-syndrome genetics cohort study (GenROC)
Background Parent/patient-reported (PRD) datasets provide ready access to phenotypic data for monogenic neurodevelopmental disorders, yet their concordance with clinical data is unclear. Methods In the GenROC study, 547 children (mean age 7.6 years, …