Categoría: JMG First
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Phenotypic description of a large French series of individuals with Potocki-Lupski syndrome
BackgroundPotocki-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 responsibl…
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Test the grandfather! Incidental in-frame DMD deletions in three asymptomatic families
The DMD gene, the largest gene in the human genome, is particularly prone to exonic deletions or duplications due to recombination events during gametogenesis, with frameshift deletions typically seen in Duchenne muscular dystrophy (DMD) and in-frame d…
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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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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 has…
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Inherited variants in autosomal dominant disease genes are a significant cause of fetal structural anomalies
BackgroundMonogenic 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 st…
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Later age of natural menopause among women with the pathogenic CHEK2 c.1100delC variant: a validation study
BackgroundThe 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 CHEK2 …
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Reclassification of variants of uncertain significance in type I collagen genes: a national reference laboratory experience
BackgroundThe 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 bu…
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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
BackgroundHeterozygous 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 ind…
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Expanding the phenotypic spectrum of MECOM-associated syndrome: rare variants are associated with syndromic pulmonary arterial hypertension
BackgroundMECOM 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. We …
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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 influe…