Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report two children who were referred for diagnostic assessment for autism and were subsequently determined to have a muscular dystrophy (MD). Each child had a history of speech delay and social impairments, but also had motor delays that had not previously been investigated. Both children met diagnostic criteria for autism spectrum disorders on standardized assessment. Each child was hypotonic and had other mild motor impairments. Serum creatine kinase (CK) activity was markedly elevated in each child, and subsequent muscle biopsy led to diagnosis of Becker's MD and congenital (autosomal recessive) MD, respectively. These cases highlight the importance of a thorough neuromotor examination for all children with suspected autism spectrum disorders.
J Autism Dev Disord 2003 Apr
PMID:Two children with muscular dystrophies ascertained due to referral for diagnosis of autism. 1275 59

Autism spectrum disorder is a genetically complex and clinically heterogeneous neurodevelopmental disorder. A recent study by the Autism Genome Project (AGP) used 1M single-nucleotide polymorphism arrays to show that rare genic copy number variants (CNVs), possibly acting in tandem, play a significant role in the genetic aetiology of this condition. In this study, we describe the phenotypic and genomic characterisation of a multiplex autism family from the AGP study that was found to harbour a duplication of exons 31-44 of the Duchenne/Becker muscular dystrophy gene DMD and also a rare deletion involving exons 1-9 of TRPM3. Further characterisation of these extremely rare CNVs was carried out using quantitative PCR, fluorescent in situ hybridisation, long-range PCR amplification and sequencing of junction fragments. The maternal chrX:32,097,213-32,321,945 tandem duplication and paternal chr9:72,480,413-73,064,196 deletion (NCBI build 36 coordinates) were transmitted to both affected boys, potentially signifying a multi-hit mechanism. The DMD reading frame rule predicts a Becker phenotype, characterised by later onset and milder symptoms. When last evaluated, neither child had developed signs of muscular dystrophy. These data are consistent with a degree of comorbidity between autism and muscular dystrophy and suggest that genomic background as well as the position of the mutation within the DMD gene may impact on the neurological correlates of Duchenne/Becker muscular dystrophy. Finally, communicating unexpected findings such as these back to families raises a number of ethical questions, which are discussed.
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PMID:A family with autism and rare copy number variants disrupting the Duchenne/Becker muscular dystrophy gene DMD and TRPM3. 2148 99

The first decades of the new medical genetics (1980 to 2000) were marked by resounding successes, with the identification of the genes responsible (when defective) for muscular dystrophy, cystic fibrosis, or Huntington's disease, to name justa few of the several thousand Mendelian genetic conditions whose causes are now known. In contrast, the search for genes involved in common disorders such as diabetes,hypertension, schizophrenia, or autism failed miserably in the 1990s, with inconsistent and conflicting results--although the strong genetic component of these diseases (that also involve environmental factors) was (and still is) beyond doubt. From 2000 on,thanks to huge progress in genomic knowledge, technology, and analytical methods, it became possible to reliably identify genes influencing the risk of complex conditions,using the so-called GWAS (Genome-Wide Association Study) approach. Yet many problems remain, such as the vexing question of the "missing heritability," or the difficulty of translating these scientific results into genetic tests with real clinical validity and utility. Autism is one of the cases in which a strong genetic component has been demonstrated, but where the search for causative genes remains difficult and attempts at developing valid genetic tests have failed, because of the many genes involved and possibly of the heterogeneity of the condition.
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PMID:Genes and non-mendelian diseases: dealing with complexity. 2534 6

Several diseases have been successfully modeled since the development of induced pluripotent stem cell (iPSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from iPSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific iPSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using iPSC modeling for Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, Phelan-McDermid, Rett syndrome as well as Nonsyndromic Autism.
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PMID:Induced pluripotent stem cells for modeling neurological disorders. 2672 48