Association between SCN5A R225Q variant and dilated cardiomyopathy: potential role of intracellular pH and WNT/β-catenin pathway

We found that the phenotype of dilated cardiomyopathy results from the interaction of genetic mutations (SCN5A R225Q variant) and environmental factors (age and other pathogenic factors), and elucidated the underlying pathogenic mechanism (elevated intercellular pH and WNT/β-catenin pathway activation). Therefore, for patients with dilated cardiomyopathy carrying some cardiac sodium channel gene mutations which might cause […]

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The International Fragile X Premutation Registry: building a resource for research and clinical trial readiness

People with the FMR1 premutation are at increased risk to develop a neurodegenerative disease (fragile X-associated tremor/ataxia syndrome, FXTAS), reproductive health problems (in females), and potentially a range of other mental and general health conditions. This paper introduces the International Fragile X Premutation Registry (IFXPR), developed to facilitate research to better understand the premutation and its impact […]

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Familial risk of epithelial ovarian cancer after accounting for gynaecological surgery: a population-based study

Family history of ovarian cancer is a strong risk factor for the disease. We observed that ovarian cancer risk is highest among women whose family members have specific types of ovarian cancer. We also described how,  as preventative surgery became more routinely recommended over time for women with an increased risk of ovarian cancer due […]

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ARMC12 mutations-a novel mechanism for human multiple midpiece-specific defects and asthenozoospermia

Asthenozoospermia is a common pathogenesis of male infertility. The motility of spermatozoa is based on the presence of an intact flagellum and an adequate energy supply. The midpiece of the human spermatozoa consists of the axoneme and the outer wrapped mitochondrial sheath, which is essential for sperm motility. Here, we identified bi-allelic ARMC12 mutations from […]

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Contribution of large genomic rearrangements in PALB2 to familial breast cancer: implications for genetic testing

Inherited mutations in PALB2 are the most common cause of familial breast cancer after BRCA1 and BRCA2 but it is possible that current clinical genetic testing might be missing some cancer-causing mutations.  For BRCA1 and BRCA2 many of the cancer-causing mutations involve changes in large sections of these genes (called large genomic rearrangements or LGRs) […]

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Identifying the psychosocial predictors of ultraviolet exposure to the face in patients with xeroderma pigmentosum

Xeroderma Pigmentosum (XP) is a genetic disease in which the system which repairs ultraviolet-induced damage is faulty. Patients develop eye and skin cancers from childhood and usually die in early adulthood. The main way to prevent the cancers and increase lifespan is extreme protection against ultraviolet in daylight, particularly for the face where the cancers […]

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Transcriptome-based variant calling and aberrant mRNA discovery enhance diagnostic efficiency for neuromuscular diseases

Precise diagnosis of the patients with neuromuscular disorders (NMD) has been hampered by the presence of many genetic loci that may give rise to heterogeneous symptoms. To enhance diagnostic yield and to further understand genetic mechanism underlying NMD, we sequenced RNA from muscle tissues from 117 Korean patients with suspected Mendelian NMDs. We called 38.1% […]

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Bi-allelic CFAP61 variants cause male infertility in humans and mice with severe oligoasthenoteratozoospermia

Oligoasthenoteratozoospermia (OAT) has become a major male infertility phenotype with a highly genetically heterogeneous. However, the genetic basis underlying most OAT cases remained to be elucidated. In this study, Hu et al. found CFAP61 variants cause OAT in humans and mice, and abnormal spermiation was present in male Cfap61-/-mice, which might be a new mechanism […]

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Heterozygous frameshift CTNNB1 variants identified in familial exudative vitreoretinopathy-affected families reveal the pathogenesis of β-catenin for the disease

Familial exudative vitreoretinopathy (FEVR) is an inheritable blinding disorder with high clinical and genetical heterogeneity. Currently, variants in fourteen genes and one locus are associated with FEVR, which accounts for only approximately 50% of the cases. This study reports three heterozygous nonsense or frameshift variants in CTNNB1 from FEVR-affected patients, which result in truncation and […]

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A polymorphic AT-repeat causes frequent allele dropout for an MME mutational hotspot exon

Pathogenic variants in the MME gene cause dominant and recessive late onset axonal hereditary neuropathy. In this study, we identified that a short increase in an AT-repeat close to two MME mutations is a frequent cause of allele dropout during Sanger sequencing causing false interpretation of the results in several of the patients. This may […]

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