Features of multiple self-healing squamous epithelioma and Loeys-Dietz syndrome in a patient with a novel TGFBR1 variant.

Multiple self-healing squamous epithelioma (MSSE, Ferguson-Smith disease) and Loeys-Dietz syndrome (LDS) are allelic conditions associated with pathogenic variants in the transforming growth factor beta receptor 1 gene (TGFBR1). We describe a patient with a novel missense variant in this gene: c.664G > A, p.

Diagnosis of Spinocerebellar Ataxias Caused by Trinucleotide Repeat Expansions.

Spinocerebellar ataxias (SCAs) are a group of disorders that are both clinically and genetically heterogeneous. They usually demonstrate onset in adulthood, but some forms may have juvenile or infantile onset. There are many different types of SCA, demonstrating different modes of inheritance and types of mutation.

Diagnosis of spinal xanthomatosis by next-generation sequencing: identifying a rare, treatable mimic of hereditary spastic paraparesis.

Cerebrotendinous xanthomatosis is an autosomal recessive disorder of bile acid metabolism causing a range of progressive neurological symptoms. Even in the presence of the classical triad of neurological dysfunction, tendon xanthoma and early onset cataracts, the diagnosis is often missed. It can mimic more common conditions such as hereditary spastic paraparesis or multiple sclerosis, particularly if the phenotype is spinal xanthomatosis where the disease causes a spastic paraplegia.

Concurrent amyotrophic lateral sclerosis and cystic fibrosis supports common pathways of pathogenesis.

Abstract We present a case of concurrent cystic fibrosis (CF) and amyotrophic lateral sclerosis (ALS). To our knowledge this is the first reported coincidence of these two diseases. Although TDP-43 dysfunction has been linked to both pathologies, it does not appear to be pivotal in this individual who does not display TDP-43 mediated aberrant splicing of the CFTR gene or carry a mutation in the TARDBP gene.

Spinocerebellar ataxias: an example of the challenges associated with genetic databases for dynamic mutations.

Locus-specific databases are an important source of information for diagnostic laboratories and a valued means of improving quality of genetic testing. Although increasingly frequent, databases for oligonucleotide repeat expansions are still scarce, due to factors that make them different and the building of databases much more difficult. Definition of what constitutes "the repeat" to measure is not a simple matter and correct sizing is not always straightforward.

A novel MPZ gene mutation in exon 2 causing late-onset demyelinating Charcot-Marie-Tooth disease.

The myelin protein zero gene (MPZ) encodes the major structural protein component of myelin in the peripheral nervous system. More than 120 mutations in MPZ have been detected so far. Clinical phenotypes include CMT1B, CMT2, Dejerine-Sottas syndrome, and congenital hypomyelination neuropathy.

Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72.

Intronic expansion of the GGGGCC hexanucleotide repeat within the C9ORF72 gene causes frontotemporal dementia and amyotrophic lateral sclerosis/motor neuron disease in both familial and sporadic cases. Initial reports indicate that this variant within the frontotemporal dementia/amyotrophic lateral sclerosis spectrum is associated with transactive response DNA binding protein (TDP-43) proteinopathy. The amyotrophic lateral sclerosis/motor neuron disease phenotype is not yet well characterized.

Consensus and controversies in best practices for molecular genetic testing of spinocerebellar ataxias.

Many laboratories worldwide are offering molecular genetic testing for spinocerebellar ataxias (SCAs). This is essential for differential diagnosis and adequate genetic counselling. The European Molecular Genetics Quality Network (EMQN) started an SCA external quality assessment scheme in 2004.

EMQN Best Practice Guidelines for molecular genetic testing of SCAs.

Other participants at the EMQN Best Practice Meeting and/or at the electronic discussions thereafter were Isabel Alonso, Anna Andersson, David Barton, Nazli Bazac, Kyproula Christodoulou, Luís Correia, Mark Davis, Mary Davis, Rob Elles, Marina Frontali, Javier Garcia-Planells, Paola Giunti, Petra Hämäläinen, Jenni Jonasson, Outi Kamarainen, Nina Larsson, Eric Leguern, Monique Losekoot, Carla Martins, Michael Morris, Clemens Müller-Reible, Simon Patton, M Luiza Saraiva-Pereira, Jorge Pinto-Basto, Beatriz Quintáns, Simon C Ramsden, Anna Ravani, Laura Rooke, Isabel Silveira, Richard Sinke, Su Stenhouse, Laura Stewart, Katrien Storm, Anna Sulek-Piatkowska, Francine Thonney, Victor Volpini, Jon Warner, Helga Weirich, Stefan Wieczorek and Christine Zühlke.