Combined genome sequencing and RNA analysis reveals and characterizes a deep intronic variant in IGHMBP2 in a patient with SMARD1

Pathogenic variants in the IGHMBP2 gene cause recessive spinal motor neuropathies of variable phenotype, including a predominantly distal motor impairment of Charcot-Marie Tooth type 2S and the more severe condition of spinal muscular atrophy with respiratory distress (SMARD1) in which infantile respiratory failure predominates.
Source: Pediatric Neurology - Category: Neurology Authors: Tags: Editorial Source Type: research

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MORC2 encodes an ATPase that plays a role in chromatin remodeling, DNA repair, and transcriptional regulation. Heterozygous variants in MORC2 have been reported in individuals with autosomal-dominant Charcot-Marie-Tooth disease type 2Z and spinal muscular atrophy, and the onset of symptoms ranges from infancy to the second decade of life. Here, we present a cohort of 20 individuals referred for exome sequencing who harbor pathogenic variants in the ATPase module of MORC2. Individuals presented with a similar phenotype consisting of developmental delay, intellectual disability, growth retardation, microcephaly, and variable...
Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Tags: Report Source Type: research
Spinal muscular atrophy (SMA 5q) is one of the most frequent autosomal recessive disease in childhood and is caused by mutations of SMN1 gene. SMA patients present with progressive muscle weakness and atrophy. SMA coexisting with another genetic entity is extremely rare and remains a diagnostic challenge. So-called "double trouble" cases demand special approach and individual multidisciplinary management. Here, we present two new cases of SMA overlapping with hereditary spastic paraplegia or Noonan syndrome, and follow-up of our previously reported patient with SMA and Charcot-Marie-Tooth 1A.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
In this study, we screened forTRPV4 mutations in a well-characterized USA cohort of 62 unrelated CMT2 patients without mutations inMFN2,GARS,NEFL, andGDAP1. All 15 coding exons ofTRPV4 were analyzed by Sanger-sequencing. Clinical features ofTRPV4-linked patients were compared with those lacking TRPV4 mutations. We identified twoTRPV4 mutations in two patients. A TRPV4-R316C was identified in a patient with family history, while a TRPV4-R269C in an apparently sporadic case. Marked clinical variations were observed in the patients withTRPV4 mutations. Our data suggest thatTRPV4-linked CMT2C accounts for a sizable fraction in...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research
CONCLUSION: Gene therapies have the potential to significantly influence the course of neuromuscular diseases. First positive intermediate results have been published and the first treatment has recently been approved in the USA. Long-term data on sustained effects and toxicity of gene therapies are not yet available. These novel treatment options will present new challenges for the healthcare systems concerning diagnosis, treatment and reimbursement. PMID: 31286145 [PubMed - as supplied by publisher]
Source: Der Nervenarzt - Category: Neurology Authors: Tags: Nervenarzt Source Type: research
Neurofilaments are components of the neuronal cytoskeleton and are composed of three subunits: the neurofilament heavy chain (NFEH), the medium chain (NEFM), and the light chain (NEFL). They are crucial for the growth of axons, the maintenance of axon caliber and the transmission of electrical impulses along axons.[1] Abnormal accumulation of neurofilament occurs in pathological conditions such as neurofilament inclusion disease (NFID), giant axonal neuropathy (GAN), diabetic neuropathy, spinal muscular atrophy (SMA), spastic paraplegia, Alzheimer's disease (AD) and Parkinson's disease (PD).
Source: Neuromuscular Disorders - Category: Neurology Authors: Tags: Case report Source Type: research
Charcot-Marie-Tooth (CMT) disease, a common inherited peripheral neuropathy, typically characterized with progressive motor and sensory polyneuropathy. It is clinically variable in its age of onset and level of severity. There are in excess of 75 genes attributed to CMT, amongst them is the Immunoglobulin-helicase- μ-binding protein 2 (IGHMBP2) gene. Pathogenic variants in IGHMBP2 is responsible for continuum between two extremes of phenotypes with fatal disorder of spinal muscular atrophy with respiratory distress type 1 (SMARD1) [1], where most infants die before 1 year of age [2] at one end and axonal prog ressive mo...
Source: Neuromuscular Disorders - Category: Neurology Authors: Tags: Case report Source Type: research
Transient receptor potential vanilloid 4 channel (TRPV4) is a calcium permeable cation channel predominantly expressed in bone and peripheral nervous system (PNS). TRPV4 mutations cause a spectrum of skeletal disorders and PNS syndromes, including Charcot-Marie-Tooth disease type 2C, spinal muscular atrophy, arthrogryposis, and scapuloperoneal spinal muscular atrophy. A 6-year-old boy from a non-consanguineous family was referred to our clinic due to arthrogryposis multiplex congenita (AMC) and weakness of lower limbs.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
This report aims to increase our awareness of SMALED and various other phenotypes associated with mutations in this gene.
Source: Polish Journal of Neurology and Neurosurgery - Category: Neurosurgery Source Type: research
Publication date: March 2018Source: Neurologia i Neurochirurgia Polska, Volume 52, Issue 2Author(s): Katarzyna Bienias, Joanna Ścibek, Joanna Cegielska, Jan KochanowskiAbstractSlowly progressive neuromuscular diseases include but are not limited to: facioscapulohumeral muscular dystrophy (FSHD) and limb-girdle muscular dystrophy (LGMD), hereditary motor and sensory neuropathy (HMSN) and spinal muscular atrophy type III (SMA3). The purpose of this study is to present an evaluation of basic and complex activities of daily living in patients suffering from these diseases.The study was conducted on a group of 58 Polish patien...
Source: Polish Journal of Neurology and Neurosurgery - Category: Neurosurgery Source Type: research
This report aims to increase our awareness of SMALED and various other phenotypes associated with mutations in this gene.
Source: Polish Journal of Neurology and Neurosurgery - Category: Neurosurgery Source Type: research
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