Titinopathies, are complex neuromuscular disorders resulting from TTN gene mutations with diverse symptoms and inheritance modes. This study focused on eight families with dominant titinopathies. We employed next genetation sequencing on DNA and RNA to identify and characterize TTN gene copy number variations (CNVs). These analyses in patients’ muscles revealed seven deletions CNVs. The prevalent […]
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Non-coding CGG repeat expansion in LOC642361/NUTM2B-AS1 is associated with a phenotype of oculopharyngodistal myopathy
Oculopharyngodistal myopathy (OPDM) is a rare neuromuscular disease characterized by progressive ptosis, ophthalmoparesis, facial/bulbar and distal weakness. CGG repeat expansions in the 5’ untranslated region of LRP12, GIPC1, NOTCH2NLC and RILPL1 have been reported to cause OPDM. In this study, we identified CGG repeat expansion in the long non-coding RNA of LOC642361/NUTM2B-AS1 in 2 unrelated […]
Genetic complexity of diagnostically unresolved Ehlers-Danlos syndrome
Ehlers-Danlos syndromes (EDS) are heritable connective tissue disorders associated with joint hypermobility, skin extensibility and tissue fragility. We report the results of whole exome sequencing and genetic burden analysis for 174 patients with complex EDS, recruited from two UK specialist clinics, who remained without a molecular diagnosis despite previous genetic testing. Ten patients were found […]
Changing the standardised obstetric care by expanded carrier screening and counselling: a multicentre prospective cohort study
This study aimed to assess the clinical significance of expanded carrier screening in the context of prenatal care by analyzing a substantial cohort. The research employed a comprehensive screening panel comprising 302 genes and utilized next-generation sequencing. The subjects were drawn from obstetric clinics, infertility centers, and medical facilities, and they received genetic counseling both […]
Spectrum of LYST mutations in Chediak-Higashi syndrome: a report of novel variants and a comprehensive review of the literature
Chediak-Higashi syndrome (CHS) is a rare genetic disorder that can cause pigmentary changes in skin, hair and eyes, easy bruising, weaker immune responses, and neurological issues secondary to abnormalities in lysosomal-related organelles. CHS arises due to variants in the LYST gene. Discerning these variants is challenging because LYST is large and its exact role is […]
Exploring the Link Between Congenital Vertebral Malformations and Neural Tube Defects
Congenital vertebral malformations (CVMs) and neural tube defects (NTDs) are common birth defects affecting the spine and nervous system due to early embryonic development issues. Our review delves into their shared embryonic origins, signaling pathways, and clinical characteristics, highlighting a significant overlap. The co-occurrence of CVMs and NTDs underscores the importance of comprehensive clinical assessments. […]
Carriers of autosomal recessive conditions: are they really ‘unaffected?’
It is currently accepted that certain genetic diseases require the inheritance of two “disease-causing” genetic variants to result in symptoms of a disease. However, some early studies suggest that the inheritance of only one of these “disease-causing” variants may result in less severe disease symptoms. People who have only one “disease-causing” variant are called carriers. […]
Recessive MECR pathogenic variants cause a LHON-like optic neuropathy
Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by subacute visual loss, typically linked to genetic defects affecting respiratory complex I genes. Here, we expand the genetic landscape of LHON by describing the first autosomal recessive case with pathogenic variants in the MECR gene. The MECR enzyme belongs to the mitochondrial fatty acid synthesis (mtFAS) […]
Association Between Genetic Polymorphisms and Risk of Adolescent Idiopathic Scoliosis in Case-Control Studies: A Systematic Review
Adolescent idiopathic scoliosis (AIS) is a lateral curvature of the spine that affects 2-3% of children and is known to have a strong genetic component. Decades of studies have revealed dozens of genetic variants that may contribute to disease risk, but these studies vary greatly in methodology, cohort demographics, and sample sizes. To critically assess […]
HnRNPR strongly represses splicing of a critical exon associated with spinal muscular atrophy through binding to an exonic AU-rich element
SMN2 exon 7 skipping is associated with spinal muscular atrophy and has been a major therapeutic target. However, the mechanism regulating exon 7 splicing remains largely unknown. This study uncovered that hnRNPR potently inhibits exon 7 inclusion through binding to an AU-rich element of the exon. Both hnRNPR and Sam68 bind to the element in […]