Exclusion of the gene locus for spinal muscular atrophy on chromosome 5q in a family with infantile olivopontocerebellar atrophy (OPCA) and anterior horn cell degeneration

Rudnik‐Schöneborn, Sabine; Wirth, Brunhilde; Röhrig, Dorothee; Saule, H; Zerres, Klaus

doi:10.1016/0960-8966(94)e0025-4

Cited by 26 publications

(14 citation statements)

References 16 publications

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“…There is no locus for the majority of the PCH1 cases and no other genes have been linked to PCH1 yet, with the exception of rare cases with TSEN54, RARS2 and VRK1 mutations (Table 2). Fifteen families with a PCH1 phenotype have been published thus far; only in 3 families mutations were identified [6,7,10,20-25,34,40,42,44-51]. Further research on these and other candidate genes in PCH1 is necessary to identify mutations involved in the remaining majority of the PCH1 cases.…”

Section: Reviewmentioning

confidence: 99%

Classification, diagnosis and potential mechanisms in Pontocerebellar Hypoplasia

Namavar

Barth

Poll-Thé

et al. 2011

Orphanet J Rare Dis

161

127

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Pontocerebellar Hypoplasia (PCH) is group of very rare, inherited progressive neurodegenerative disorders with prenatal onset. Up to now seven different subtypes have been reported (PCH1-7). The incidence of each subtype is unknown. All subtypes share common characteristics, including hypoplasia/atrophy of cerebellum and pons, progressive microcephaly, and variable cerebral involvement. Patients have severe cognitive and motor handicaps and seizures are often reported. Treatment is only symptomatic and prognosis is poor, as most patients die during infancy or childhood. The genetic basis of different subtypes has been elucidated, which makes prenatal testing possible in families with mutations. Mutations in three tRNA splicing endonuclease subunit genes were found to be responsible for PCH2, PCH4 and PCH5. Mutations in the nuclear encoded mitochondrial arginyl- tRNA synthetase gene underlie PCH6. The tRNA splicing endonuclease, the mitochondrial arginyl- tRNA synthetase and the vaccinia related kinase1 are mutated in the minority of PCH1 cases. These genes are involved in essential processes in protein synthesis in general and tRNA processing in particular. In this review we describe the neuroradiological, neuropathological, clinical and genetic features of the different PCH subtypes and we report on in vitro and in vivo studies on the tRNA splicing endonuclease and mitochondrial arginyl-tRNA synthetase and discuss their relation to pontocerebellar hypoplasia.

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Section: Reviewmentioning

confidence: 99%

Classification, diagnosis and potential mechanisms in Pontocerebellar Hypoplasia

Namavar

Barth

Poll-Thé

et al. 2011

Orphanet J Rare Dis

161

127

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“…Homozygous deletion of SMN1 was indeed observed in atypical forms of SMA including those associated with congenital heart defects, arthrogryposis, or, in some patients, those affected with congenital axonal neuropathy or an adult form of SMA 6, 11, 13, 23, 53, 104. In contrast, neither deletion of the SMN1 gene nor linkage to chromosome 5q has been observed in SMA associated with diaphragmatic involvement, SMA with olivopontocerebellar atrophy, the autosomal dominant form of SMA, or the post‐polio syndrome 2, 43, 49, 75, 89. Although SMN1 gene deletion testing has allowed accurate prenatal prediction, the genomic complexity of the region and its high degree of variability have hampered the ability to directly detect the SMA carriers.…”

Section: Genetic Basis Of Childhood Proximal Sma: An Unusual Genetic mentioning

confidence: 99%

Spinal muscular atrophy: Recent advances and future prospects

et al. 2002

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Spinal muscular atrophies (SMA) are characterized by degeneration of lower motor neurons associated with muscle paralysis and atrophy. Childhood SMA is a frequent recessive autosomal disorder and represents one of the most common genetic causes of death in childhood. Mutations of the SMN1 gene are responsible for SMA. The knowledge of the genetic basis of SMA, a better understanding of SMN function, and the recent generation of SMA mouse models represent major advances in the field of SMA. These are starting points towards understanding the pathophysiology of SMA and developing therapeutic strategies for this devastating neurodegenerative disease, for which no curative treatment is known so far.

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“…Neuropathological findings include degeneration of anterior horn cells, inferior olives, pons, and neocerebellum with fragmentation or destruction of the dentate, prominent gliosis, and cerebellar foliation abnormalities. The thalami and basal ganglia may also be affected [Rudnik-Schoneborn et al, 1995].…”

Section: Differential Diagnosis Of (O)pchmentioning

confidence: 99%

“…Their distinguishing features on MRI are pontine and cerebellar hypoplasia with relative preservation of the vermis. PCH-1 is the combination of PCH and spinal anterior horn degeneration (reviewed in [Rudnik-Schoneborn et al, 1995]; OMIM #607596). Infants typically present with Werdnig-Hoffman-like symptoms, congenital large joint contractures, arreflexia, and severe hypotonia, although this may evolve into hypertonia [Salman et al, 2003].…”

Section: Differential Diagnosis Of (O)pchmentioning

confidence: 99%

Severe, fetal‐onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5?

Patel

Becker

Toi

et al. 2006

American J of Med Genetics Pt A

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We present three siblings with a precise onset of fetal seizure-like activity who had severe olivopontocerebellar hypoplasia (OPCH) and degeneration. Autopsies at 20, 27, and 37 weeks gestation showed diffuse central nervous system volume loss that was most marked for the cerebellum and brain stem structures. Neuropathological abnormalities included dysplastic, C-shaped inferior olivary nuclei, absent or immature dentate nuclei, and cell paucity more marked for the cerebellar vermis than the hemispheres. Delayed development was seen in layer 2 of the cerebral cortex and in Purkinje cells of the cerebellum. Prenatal monitoring defined a developmental window of 16-18 weeks gestation when ultrasonic assessment of cerebellar width was used for prenatal diagnosis. We discuss our findings in the context of the differential diagnosis for infantile (O)PCH and propose a classification scheme for the pontocerebellar hypoplasias. These patients represent the earliest reported with OPCH and provide unique information regarding the developmental neuropathology of this condition.

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Exclusion of the gene locus for spinal muscular atrophy on chromosome 5q in a family with infantile olivopontocerebellar atrophy (OPCA) and anterior horn cell degeneration

Cited by 26 publications

References 16 publications

Classification, diagnosis and potential mechanisms in Pontocerebellar Hypoplasia

Classification, diagnosis and potential mechanisms in Pontocerebellar Hypoplasia

Spinal muscular atrophy: Recent advances and future prospects

Severe, fetal‐onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5?

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