Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour

Testicular cancer is the most common cancer affecting young men and, like many other adult-onset cancers, multiple-case families do occur.  The genetic architecture of familial and sporadic cancers often differs, with rare, highly-penetrant mutations causing the former, and multiple common low-penetrance genetic variants underlying the latter. The study by Kratz and colleagues investigated familial testicular […]

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Chromosome fragility in Fanconi anemia patients: diagnostic implications and clinical impact

Fanconi anemia (FA) is a rare syndrome characterized by bone marrow failure, malformations, and cancer predisposition. Chromosome fragility induced by DNA interstrand crosslink (ICL)-inducing drugs is the gold standard diagnostic test for FA. We present data from 198 chromosome fragility tests and propose a new chromosome fragility index that provides a cut-off diagnostic level to […]

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Maternally transmitted late-onset nonsyndromic deafness is associated with the novel heteroplasmic T12201C mutation in the mitochondrial tRNAHis gene

A specific genetic defect in one Chinese family shows that hearing loss was inherited from the female parent.  The defect results from a point mutation — the substitution of a single DNA “base” for another during replication — in the genes of a tiny cellular organ called the mitochondria, which generates a cell’s energy. When […]

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Facioscapulohumeral muscular dystrophy: new insights from compound heterozygotes and implication for prenatal genetic counselling

Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary muscle disease affecting approximately 1 in 20,000 individuals.  The genetic defect associated with FSHD does not reside in any protein-coding gene.  Instead, FSHD had previously been correlated with a specific set of DNA variations (termed haplotype) at 4q35. Using genetic and clinical information from the Italian National Registry […]

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Mutations in PRRT2 result in paroxysmal dyskinesias with marked variability in clinical expression

Paroxysmal dyskinesias (PD) are a group of neurological disorders with episodes of involuntary movements that can be classified into three main categories: paroxysmal kinesigenic dyskinesia (PKD) , paroxysmal exercise induced dyskinesia (PED) and paroxysmal nonkinesigenic dyskinesia(PNKD). Interestingly, PDs may be variably associated with epilepsy. Description of familial infantile convulsions with paroxysmal choreoathetosis (ICCA) and its […]

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Complete loss of expression of the ANT1 gene causing cardiomyopathy and myopathy.

Mitochondrial disorders are a significant cause of morbidity and mortality in the population. Here, we describe an adult patient with autosomal recessive myopathy and cardiomyopathy resulting from a complete loss of expression of the ADP/ATP translocase 1 (ANT1), a mitochondrial molecule which mediates ADP/ATP exchange between cytosol and mitochondria through the inner mitochondrial membrane. Skeletal […]

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A bias-reducing pathway enrichment analysis of genome-wide association data confirmed association of the MHC region with schizophrenia

Complex diseases are often caused by many genetic markers or genes, thus, pathway-based or gene-based analysis of genome-wide association study (GWAS) data becomes an important approach to studying the underlying molecular mechanisms. A critical issue in this approach is the gene length bias – long genes tend to have more SNPs investigated and, thus, have […]

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A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation

The concept of the testicular dysgenesis syndrome (TDS) suggests that male infertility, cryptorchidism, hypospadias, impaired spermatogenesis and testicular germ cell cancer often have a common origin. In a systems biology framework, by combining a genome-wide association study with gene expression and mouse knock-out data to study the genetic components that predispose to TDS, we identified […]

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