Etiqueta: #JMedGenet
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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…
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Novel in-frame variant in DES (p.Glu353dup) causes myofibrillar myopathy: clinical, in silico and functional studies
Background Desmin (DES) is a major intermediate filament protein involved in the structural integrity and function of striated muscles. Pathogenic mutations in DES are predominantly missense variants, causing isolated cardiomyopathy and combinations o…
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Targeting autophagy in Duchenne muscular dystrophy: mechanistic insights and emerging therapeutic strategies
Duchenne muscular dystrophy (DMD) is a severe X-linked myopathy characterised by progressive skeletal and cardiac muscle degeneration, loss of ambulation, respiratory failure and premature mortality. Although corticosteroids and gene therapies have im…
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Refining the phenotypic spectrum of PNKP-related microcephaly: a study of 27 new patients
Background Biallelic pathogenic variants in PNKP are associated with microcephaly and early-onset seizures (MCSZ), ataxia with oculomotor apraxia type 4 and Charcot-Marie-Tooth disease type 2B2. Methods We describe the clinical and neuroimaging featu…
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Catatonia and regression in an autism spectrum disorder patient harbouring a BRSK2 frameshift mutation
Deleterious variants in the BRSK2 gene, which encodes a serine/threonine kinase crucial for neuronal polarisation and brain development, have recently been linked to the pathogenesis of autism spectrum disorder (ASD). However, comprehensive clinical d…
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Obstetric history of women with m.3243A>G: an observational cohort study
Background Mitochondrial diseases are genetic disorders arising from pathogenic variants in nuclear or mitochondrial DNA (mtDNA) characterised by respiratory chain dysfunction. Clinical manifestations are diverse, and treatment is mostly symptomatic. …