12 Result(s)
within
N. Simon Thomas
Biomedicine
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Article
Open AccessTargeting de novo loss-of-function variants in constrained disease genes improves diagnostic rates in the 100,000 Genomes Project
Genome sequencing was first offered clinically in the UK through the 100,000 Genomes Project (100KGP). Analysis was restricted to predefined gene panels associated with the patient’s phenotype. However, panels...
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Article
Open AccessA systematic analysis of splicing variants identifies new diagnoses in the 100,000 Genomes Project
Genomic variants which disrupt splicing are a major cause of rare genetic diseases. However, variants which lie outside of the canonical splice sites are difficult to interpret clinically. Improving the clinic...
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Article
Open AccessEvidence that the Ser192Tyr/Arg402Gln in cis Tyrosinase gene haplotype is a disease-causing allele in oculocutaneous albinism type 1B (OCA1B)
Oculocutaneous albinism type 1 (OCA1) is caused by pathogenic variants in the TYR (tyrosinase) gene which encodes the critical and rate-limiting enzyme in melanin synthesis. It is the most common OCA subtype foun...
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Article
Open AccessWhole genome sequencing in the diagnosis of primary ciliary dyskinesia
It is estimated that 1–13% of cases of bronchiectasis in adults globally are attributable to primary ciliary dyskinesia (PCD) but many adult patients with bronchiectasis have not been investigated for PCD. PCD...
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Article
Open AccessA CRISPR and high-content imaging assay compliant with ACMG/AMP guidelines for clinical variant interpretation in ciliopathies
Ciliopathies are a broad range of inherited developmental and degenerative diseases associated with structural or functional defects in motile or primary non-motile cilia. There are around 200 known ciliopathy...
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Article
Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction
Recent studies have identified PRDM9, a zinc finger (ZF) protein, as a key regulator of meiotic recombination. As both recurrent genomic disorders and chromosomal non-disjunction are known to be associated with s...
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Article
Breakpoint map** and haplotype analysis of three reciprocal translocations identify a novel recurrent translocation in two unrelated families: t(4;11)(p16.2;p15.4)
The majority of constitutional reciprocal translocations appear to be unique rearrangements arising from independent events. However, a small number of translocations are recurrent, most significantly the t(11...
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Article
Investigation of the origins of human autosomal inversions
A significant proportion of both pericentric and paracentric inversions have recurrent breakpoints and so could either have arisen through multiple independent events or be identical by descent (IBD) with a si...
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Article
Parental and chromosomal origin of unbalanced de novo structural chromosome abnormalities in man
We report the parental origin, and where possible the chromosomal origin of 115 de novo unbalanced structural chromosome abnormalities detectable by light microscopy. These consisted of 39 terminal deletions, ...
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Article
Functional disomy resulting from duplications of distal Xq in four unrelated patients
Duplications involving the X chromosome, in which the duplicated region is not subject to inactivation, are rare. We describe four distal Xq duplications, in three males and one female, in which the duplicated...
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Article
Open AccessDosage analysis of cancer predisposition genes by multiplex ligation-dependent probe amplification
Multiplex ligation-dependent probe amplification (MLPA) is a recently described method for detecting gross deletions or duplications of DNA sequences, aberrations which are commonly overlooked by standard diag...
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Article
A study of females with deletions of the short arm of the X chromosome
We have undertaken a clinical and molecular study of 25 females with deletions of the short arm of the X chromosome. We have determined the deletion breakpoints, the parental origin and the activation status o...
