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 […]
Latest articles
Exploring the Link Between Congenital Vertebral Malformations and Neural Tube Defects (Contributed by Dr Nan Wu)
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?’ (Contributed by Drs. Justine Keathley and Amber Hames)
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 (Contributed by Dr. Claudio Fiorini)
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 […]
Association Between Genetic Polymorphisms and Risk of Adolescent Idiopathic Scoliosis in Case-Control Studies: A Systematic Review (Contributed by Liz Terhune, MS)
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 (Contributed by Tao Jiang)
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 (Contributed by Dr Mathilde Filser)
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 (Contributed by María Justel)
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 (Contributed by Dr. Zhengwei Yuan)
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 (Contributed by Dr Richard D Bagnall)
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. […]