Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies.

encodes a conserved membrane protein that stabilizes the junctions of the tubular endoplasmic reticulum network playing crucial roles in diverse biological functions. Recently, homozygous variants in were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying developmental delay, epilepsy and nonspecific brain malformations including corpus callosum hypoplasia and variable impairment of cerebellum. We sought to delineate the molecular and phenotypic spectrum of -related disorder.

Systematic identification of disease-causing promoter and untranslated region variants in 8,040 undiagnosed individuals with rare disease.

Background: Both promoters and untranslated regions (UTRs) have critical regulatory roles, yet variants in these regions are largely excluded from clinical genetic testing due to difficulty in interpreting pathogenicity. The extent to which these regions may harbour diagnoses for individuals with rare disease is currently unknown.

Methods: We present a framework for the identification and annotation of potentially deleterious proximal promoter and UTR variants in known dominant disease genes.

Prediagnosis pathway benchmarking audit in patients with Duchenne muscular dystrophy.

Objective: To describe age and time at key stages in the Duchenne muscular dystrophy (DMD) prediagnosis pathway at selected centres to identify opportunities for service improvement.

Design: A multicentre retrospective national audit.

Setting: Nine tertiary neuromuscular centres across the UK and Ireland.

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy.

Objective: To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene.

Methods: Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1.

Results: We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations.

A type I interferon signature identifies bilateral striatal necrosis due to mutations in ADAR1.

Background: We recently observed mutations in ADAR1 to cause a phenotype of bilateral striatal necrosis (BSN) in a child with the type I interferonopathy Aicardi-Goutières syndrome (AGS). We therefore decided to screen patients with apparently non-syndromic BSN for ADAR1 mutations, and for an upregulation of interferon-stimulated genes (ISGs).

Methods: We performed Sanger sequencing of ADAR1 in a series of patients with BSN presenting to us during our routine clinical practice.

Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study.

Background: Aicardi-Goutières syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR). The disease is severe and effective treatments are urgently needed. We investigated the status of interferon-related biomarkers in patients with AGS with a view to future use in diagnosis and clinical trials.

Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder.

Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members.

Acquired transverse myelopathy in children in the United Kingdom--a 2 year prospective study.

Aims: To define the incidence, describe presentation, management and outcome and identify prognostic factors in Acquired Transverse Myelopathy (ATM) in children under 16 years.

Methods: A prospective population-based surveillance study, involving all consultant paediatric neurologists in the United Kingdom from 1 July 2002 to 30 June 2004.

Results And Discussion: Response rate was 91%, and 60 children were reported, of whom 41 were included.

Severe progressive late onset myelopathy and arachnoiditis following neonatal meningitis.

This case series describes four children who had meningitis in the neonatal period. After a stable period of years, they developed a myelopathy caused by chronic arachnoiditis. The myelopathy was precipitated by a fall in two cases, and in two cases there was an acute deterioration after surgery.

Muscle biopsy without centrally located nuclei in a male child with mild X-linked myotubular myopathy.

In children with a myopathy, muscle biopsy, together with the clinical presentation, can guide further investigations. The presence of centrally located nuclei suggests a myotubular myopathy, and gene testing may confirm this diagnosis. We describe a male child with a mild form of X-linked myotubular myopathy for which repeated muscle biopsy did not show the characteristic pattern of centrally located nuclei.