Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pontocerebellar hypoplasia is a heterogeneous group of disorders characterized by abnormally small cerebellum and brainstem. Pontocerebellar hypoplasia type 1 is associated with spinal anterior horn cell degeneration, microcephaly, congenital contractures, polyhydramnios, and respiratory insufficiency leading to death in infancy. Recently, however, the spectrum of this disease has been extended to include less severe variants, some of which are associated with minimal atrophy of the brainstem. In two reported cases of late-onset variant pontocerebellar hypoplasia, the siblings were alive at 9 years and 6 years, respectively, but were severely crippled and anarthric; they had features of anterior horn cell involvement and cerebellar atrophy but the brainstem was spared. The present case is that of a 12-year-old boy with early onset of anterior horn cell involvement and slowly progressive cerebellar ataxia who is still able to walk with support and speak in sentences. He was found to be devoid of the exon 7 and exon 8 deletion of the survival motor neuron gene seen in classical spinal muscular atrophy, and magnetic resonance imaging indicated marked atrophy of the cerebellar vermis and hemispheres, with minimal involvement of the brainstem. This form is apparently the mildest variant of pontocerebellar hypoplasia type 1 described to date.
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PMID:A mild variant of pontocerebellar hypoplasia type 1 in a 12-year-old Indian boy. 1930 45

Pontocerebellar hypoplasia type 1 (PCH1) is a major cause of non-5q spinal muscular atrophy (SMA). We screened 128 SMN1-negative SMA patients from Bulgaria for a frequent mutation -p.G31A in EXOSC3, and performed a literature review of all genetically verified PCH1 cases. Homozygous p.G31A/EXOSC3 mutation was identified in 14 Roma patients, representing three fourths of all our SMN1-negative Roma SMA cases. The phenotype of the p.G31A/EXOSC3 homozygotes was compared to the clinical presentation of all reported to date genetically verified PCH1 cases. Signs of antenatal onset of disease present at birth were common in all PCH1 sub-types except in the homozygous p.D132A/EXOSC3 patients. The PCH1sub-types with early death (between ages 1 day and 17 months), seen in patients with p.G31A/EXOSC3 or SLC25A46 mutations have a SMA type 1-like clinical presentation but with global developmental delay, visual and hearing impairment, with or without microcephaly, nystagmus and optic atrophy. Mutations with milder presentation (homozygous p.D132A/EXOSC3 or VRK1) may display additionally signs of upper motor neuron impairment, dystonia or ataxia and die at age between 5 and 18 years. Other EXOSC3 mutations and EXOSC8 cases are intermediate - SMA type 1-like presentation, spasticity (mostly in EXOSC8) and death between 3 months and 5 years. There is no correlation between neurological onset and duration of life. We add marble-like skin and congenital laryngeal stridor as features of PCH1. We show that imaging signs of cerebellar and pontine hypoplasia may be missing early in infancy. EMG signs of anterior horn neuronopathy may be missing in PCH1 patients with SLC25A46 mutations. Thus, there is considerable phenotypic variability in PCH1, with some cases being more SMA-like, than PCH-like. Detailed clinical evaluation and ethnicity background may guide genetic testing and subsequent genetic counseling.
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PMID:Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature. 2965 27

Pontocerebellar hypoplasia (PCH) encompasses a group of neurodegenerative disorders. There are ten known subtypes with common characteristics of pontine and cerebellar hypoplasia or atrophy, neocortical atrophy, and microcephaly. PCH is associated with anterior horn cell degeneration in PCH1a and PCH1b due to mutations in the VRK1 and EXOSC3 genes. Late onset PCH1 has been described in single case reports. The molecular etiology remains mostly unknown. We describe two siblings from a consanguineous Moslem Arabic family with a unique combination of progressive cerebellar atrophy and a SMA-like anterior horn cell degeneration due to a homozygous mutation in the PLA2G6 gene (NM_003560.2). The PLA2G6 gene encodes phospholipase A2 beta, which is involved in the remodeling of membrane phospholipids, signal transduction and calcium signaling, cell proliferation and apoptosis. Mutations in PLA2G6 are known to cause Neurodegeneration with brain iron accumulation 2 (NBIA2): Our patients have some similarities with NBIA2; both are characterized by rapidly progressive psychomotor regression and cerebellar atrophy. However, NBIA2 is not known to exhibit anterior horn cell degeneration. Our patients' phenotype is more consistent with late onset PCH1; thus, indicating that the spectrum of clinical and radiological presentations of PLA2G6 mutations should be extended and that this gene should be included in the molecular evaluation of patients with late onset PCH1.
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PMID:Infantile onset progressive cerebellar atrophy and anterior horn cell Degeneration-A novel phenotype associated with mutations in the PLA2G6 gene. 3168 48