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) […]
Latest articles
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 […]
Adaptive Nanopore sequencing to determine pathogenicity of BRCA1 exonic duplication
The diagnosis of hereditary breast and ovarian cancer is based on the detection of germline alterations in BRCA1 among other genes. However, structural variants can be difficult to assess with standard molecular techniques. In the recent years, Oxford Nanopore long-read sequencing has proved its relevance to accurately and rapidly provide genetic diagnoses of these types […]
Expanding the phenotypic spectrum of TRAPPC11-related muscular dystrophy: 25 Roma individuals carrying a founder variant
Limb-girdle muscular dystrophies (LGMD) are muscle disorders with a genetic cause. TRAPCC11 is one of the many genes involved in LGMD, which leads to muscle weakness from early childhood, intellectual disability and elevated muscle enzymes in blood test, among other symptoms. In this study, we report 25 Roma individuals who share the same homozygous variant […]
Mutations in VWA8 cause autosomal-dominant retinitis pigmentosa via aberrant mitophagy activation
Retinitis pigmentosa (RP) is the most common hereditary retinal dystrophy. This study identified variant c.3070G>A;c.4558C>T (p.Gly1024Arg; p.Arg1520Ter) in VWA8 which is linked to retinal diseases from a four generation Chinese family with autosomal dominant retinitis pigmentosa. Then this study showed that the VWA8 variant can induce mitochondrial defects, resulting in the activation of mitophagy and […]
TBX20 loss-of-function variants in families with left ventricular non-compaction cardiomyopathy
TBX20 gene encodes a transcription factor that is essential for heart development. Recent experimental data implicate loss of TBX20 function in the development of left ventricular noncompaction cardiomyopathy (LVNC) but supporting clinical and genetic data in affected families is scarce. We report a series of four families with TBX20 loss-of-function variants that segregate with LVNC. […]
Opportunistic genetic screening increases the diagnostic yield and is medically valuable for care of patients and their relatives with hereditary cancer
Patients with suspicion of hereditary cancer are referred to cancer genetic counselling units, where they are assessed for genetic testing suitability. If so, those genes known to be associated with specific cancer or syndrome predisposition are analysed by a state-of-the-art technology known as next-generation sequencing (NGS). Additionally, NGS enables the analysis of a broad range […]
Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature
KBG syndrome is a rare neurodevelopmental disorder caused by heterozygous variants in the ANKRD11 gene and is one of the most prevalent genetic syndromes. Many reports over the years have delineated the variable phenotypic spectrum of this condition but the skeletal and in particular the neuroimaging features remain poorly defined. We have systematically analyzed the […]
Genetic and phenotypic spectrum of non-21-hydroxylase-deficiency primary adrenal insufficiency in childhood: data from 111 Chinese patients
Primary adrenal insufficiency (PAI) is a rare but life-threatening condition. We retrospectively analyzed the genetic and clinical characteristics of 111 non-21OHD PAI patients in China. STAR and NR0B1 were the most frequently mutated genes in Chinese patients with non-21OHD PAI. The age of onset was dependent on etiology. Clinical characteristics (17OHP, VLCFA, external genitalia, blood […]