Two patients with MIRAGE syndrome lacking haematological features: role of somatic second-site reversion SAMD9 mutations

MIRAGE syndrome is a life-threatening congenital disorder caused by deleterious SAMD9 mutations. In MIRAGE syndrome patients, multiple organ systems, including the haematopoietic system, are affected. We experienced two atypical MIRAGE syndrome patients who did not have any haematopoietic problems. In leukocyte DNA samples of the two patients, not only a deleterious SAMD9 mutation, but also […]

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Missense variants in the chromatin remodeler CHD1 are associated with neurodevelopmental disability

CHD1 is a chromatin remodeler which plays a role in ensuring chromatin accessibility across the genome in stem cells. Here we report that novel missense variants in CHD1 are associated with a neurodevelopmental phenotype that includes autism, speech apraxia and hypotonia. CHD1 has not previously been associated with such a phenotype and, interestingly, the location […]

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New insights into SERCA2a gene therapy in heart failure: pay attention to the negative effects of B-type natriuretic peptides

Heart failure (HF) is an end-stage cardiovascular disease with high rates of hospitalization and mortality. SERCA2a Gene therapy is a novel potential method for treating HF. CUPID is the first phase 1/2 study to assess the effects of SERCA2a gene transfer on patients with HF. However, though promising results were observed in CUPID 1, SERCA2a […]

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Comprehensive analysis of the MLH1 promoter region in 480 colorectal cancer patients and 1,150 controls reveals new variants including one with a heritable constitutional MLH1 epimutation

Most MLH1 germline defects predisposing for Lynch Syndrome constitute sequence changes or deletions in the coding region. Searching for variants in the MLH1 promoter causative for silencing or methylation, we sequenced the extended MLH1 promoter region for 480 colorectal cancer patients and 1,150 controls. We detected ten rare promoter variants. One was found in in […]

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Genome-wide association study identifies ERBB4 on 2q34 as a novel locus associated with sperm motility in Japanese men

A decline in sperm motility is greatly influential on fertilization efficiency. Sperm motility is affected not only by lifestyle and environmental factors but also by genetic factors. However, the genetic influences upon individual differences in sperm motility remain unknown. We have conducted a genome-wide association study (GWAS) in Japanese men, to clarify the genetic determinants […]

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Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss

Hearing loss is a common sensory defect that can significantly impact quality of life. The majority of congenital cases are attributable to genetic factors. To date, more than one hundred deafness genes have been reported. Using whole exome sequencing and linkage analysis, we identified a heterozygous variant, c.296G>A, in IFNLR1 as a strong candidate deafness […]

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Evidence for genetic anticipation in von Hippel-Lindau syndrome

Von Hippel-Lindau syndrome (vHL) is a hereditary cancer syndrome that predisposes to developing tumours in multiple organs. Initiating tumour surveillance before tumours are likely to occur is critical for optimal patient outcomes. In our study, we found significantly earlier ages of tumour onset in children with vHL compared to their vHL parents, indicating vHL may exhibit genetic anticipation (where symptoms […]

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Chromothripsis and ring chromosome 22: a paradigm of genomic complexity in the Phelan-McDermid syndrome (22q13 deletion syndrome)

Ring chromosomes with a highly complex structure derived by chromoanasynthesis events have been so far reported in only in cancer. We show that a germline ring chromosome 22, detected in a child with a severe neurodevelopmental disorder, was in fact the product of a de novo catastrophic event producing the deletion of the distal 22q13 […]

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Catalogue of inherited disorders found among the Irish Traveller population

Irish Travellers are an endogamous nomadic population, numbering up to 40,000, on the island of Ireland. Their origins are unclear but date back centuries. The Irish Government awarded Irish Travellers ethnicity status in March 2017. There are smaller populations of Irish Travellers living in Europe & USA. As they practice consanguinity, many rare inherited disorders […]

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