Etiqueta: #JMedGenet
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Mosaic variegated aneuploidy as a novel feature in patients with Mulibrey nanism and TRIM37 variants
Mulibrey nanism is a rare disorder caused by biallelic tripartite motif containing protein 37 (TRIM37) variants and characterised by prenatal onset growth failure, dysmorphic features, restrictive heart disease and predisposition to tumours. TRIM37 ha…
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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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Reclassification of variants of uncertain significance in type I collagen genes: a national reference laboratory experience
Background The availability of large volumes of data from genetic testing has enabled the interpretation of more DNA variants, contributing to a greater number of identified variants of uncertain significance (VUS). The growing number of VUS causes a …
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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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Expanding the phenotypic spectrum of MECOM-associated syndrome: rare variants are associated with syndromic pulmonary arterial hypertension
Background MECOM encodes a developmental and haematopoietic transcription factor associated with a rare early-onset syndrome including bone marrow failure, skeletal and other congenital anomalies. Heterozygous de novo variants are the primary cause….
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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, …
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Clinical manifestations of chromosome 19p13.11 duplication
Background Chromosome 19 is the most gene-dense chromosome in the human genome, with a high frequency of segmental duplications that predispose it to genomic rearrangements. While deletions of chromosome 19 have been associated with various clinical c…
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Biallelic TTBK1 variant causes a severe syndromic neurodevelopmental disorder: clinical and genetic insights from two siblings
Background Tau-tubulin kinase 1 (TTBK1) is a neuron-enriched kinase implicated in phosphorylation and neurodegeneration. Human phenotypes associated with constitutional TTBK1 variants remain undefined. Methods Two siblings with a severe neurodevelop…