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BACKGROUND Mucolipidosis type IV (MLIV) is an autosomal recessive disease caused by mutations in the MCOLN1 gene that codes for mucolipin, a member of the transient receptor potential (TRP) gene family. OBJECTIVE To comprehensively characterize the clinical and genetic abnormalities of MLIV. METHODS Twenty-eight patients with MLIV, aged 2 to 25 years,(More)
BACKGROUND Huntington's disease (HD) is a rare triplet repeat (CAG) disorder. Advanced, multi-centre, multi-national research frameworks are needed to study simultaneously multiple complementary aspects of HD. This includes the natural history of HD, its management and the collection of clinical information and biosamples for research. METHODS We report(More)
Eight severe inherited neurodegenerative diseases are caused by expansion of glutamine repeats in the affected proteins. In every case, proteins with repeats of fewer than 38 glutamine residues are harmless, but those with repeats of more than 41 glutamine residues form toxic neuronal nuclear aggregates in the affected neurons. Similarly, proteins that have(More)
Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. Filamin A, encoded by the gene FLNA, is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. We identified localized mutations in FLNA that conserve the(More)
OBJECTIVE To obtain penetrance data for Huntington's disease when DNA results are in the range of 36-39 CAG repeats and assess the consistency of reporting the upper allele from two reference centres. METHOD Data were collected anonymously on age of onset or age last known to be unaffected from a cohort of individuals with results in this range. DNA(More)
The severe mental retardation and speech deficits associated with 22q13 terminal deletions have been attributed in large part to haploinsufficiency of SHANK3, which maps to all 22q13 terminal deletions, although more proximal genes are assumed to have minor effects. We report two children with interstitial deletions of 22q13 and two copies of SHANK3, but(More)
Familial visceral neuropathy (FVN) is a heterogeneous group of disorders due to abnormalities of the myenteric plexus. FVN with neuronal intranuclear inclusions is one particular form of FVN with a variable phenotype that includes achalasia, gastro-esophageal reflux, intestinal dysmotility and pseudo-obstruction, dysarthria, peripheral neuropathy and(More)
The pedigrees of 192 subjects at risk of Duchenne or Becker muscular dystrophy, myotonic dystrophy, or balanced chromosome translocations attending three regional genetic clinics were inspected to identify relatives who were themselves at high risk of these disorders. Of the 342 relatives eligible for inclusion, 43% (63/147) of the register relatives and(More)
Wolf-Hirschhorn syndrome is caused by anomalies of the short arm of chromosome 4. About 55% of cases are due to de novo terminal deletions, 40% from unbalanced translocations and 5% from other abnormalities. The facial phenotype is characterized by hypertelorism, protruding eyes, prominent glabella, broad nasal bridge and short philtrum. We used dense(More)
The ascertained prevalence of Huntington's disease (HD) increased significantly following the provision of diagnostic testing. A systematic review was conducted to estimate the prevalence of HD in the post-diagnostic testing era. 22 studies with original data pertaining to the prevalence of HD (1993-2015) were included and analyzed. A global meta-analysis(More)