Categoría: Open access
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Genetic and embryonic transcriptome analyses reveal the molecular and developmental basis of Mayer-Rokitansky-Küster-Hauser syndrome
BackgroundMayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterised by aplasia of the uterus, cervix and upper part of the vagina. The genetic aetiology remains incompletely understood.MethodsWe performed gene-level and gene set-level bu…
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No association of Alzheimer disease with the joint effect of HFE and TF in the mid-western Amish
Variants in iron metabolism genes have been implicated in Alzheimer Disease (AD) pathogenesis.1 2 Previous studies suggested that the joint effect of haemochromatosis (HFE) C282Y (rs1800562) and transferrin (TF) C2 (P589S, rs1049296) variants increases…
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Recontact and follow-up for individuals with germline pathogenic variants in hereditary breast and ovarian cancer susceptibility genes: a UK Cancer Genetics Group consensus meeting
Background Routine genetic testing for germline pathogenic variants (GPVs) in cancer susceptibility genes (CSGs) in individuals with suspected hereditary cancer risk, and subsequent cascade testing in close relatives, has led to a significantly increa…
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Health-related quality of life in patients with mitochondrial disease and their carers
Background Mitochondrial diseases are a group of rare, chronic disorders with a significant disease burden; however, there is limited knowledge about their effects on the health-related quality of life (HRQoL) of patients and their carers. This study …
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Heterozygous TBX2 frameshift variants cause a novel syndromic hearing loss with incompletely penetrant nystagmus
Background A substantial fraction of hereditary hearing loss (HL) remains unexplained by known HL genes. Tbx2 is a developmental transcription factor critical for inner ear hair cell differentiation in mice, while its pathogenic role in genetic HL in …
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Molecular diagnosis, clinical evaluation and phenotypic spectrum of Townes-Brocks syndrome: insights from a large Chinese hearing loss cohort
BackgroundTownes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and recognition of TBS can be challenging and there has been a lack of investigation of…
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BTB domain mutations perturbing KCTD15 oligomerisation cause a distinctive frontonasal dysplasia syndrome
IntroductionKCTD15 encodes an oligomeric BTB domain protein reported to inhibit neural crest formation through repression of Wnt/beta-catenin signalling, as well as transactivation by TFAP2. Heterozygous missense variants in the closely related paralog…
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Heterozygous deletion of HOXC10-HOXC9 causes lower limb abnormalities in congenital vertical talus
Genes involved in limb patterning are sensitive to the gene dosage effect.1 In this brief communication, we examine the possible associations between the heterozygous deletion of HOXC10-HOXC9 and congenital vertical talus (CVT). In 2016, Alvarado et al…
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Variant reclassification and clinical implications
Genomic technologies have transformed clinical genetic testing, underlining the importance of accurate molecular genetic diagnoses. Variant classification, ranging from benign to pathogenic, is fundamental to these tests. However, variant reclassificat…
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Childhood-onset hypertrophic cardiomyopathy caused by thin-filament sarcomeric variants
Up to 20% of children with sarcomeric hypertrophic cardiomyopathy (HCM) have disease-causing variants in genes coding for thin-filament proteins. However, data on genotype-phenotype correlations for thin-filament disease are limited. This study describ…