Boucher–Neuhäuser syndrome : cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism ; two novel cases and a review of 40 cases from the literature
| Autor: | Christina Gerth-Kahlert, Dominik Straumann, Matthis Synofzik, Peter Bauer, Florian Harmuth, Dagmar Timmann, Alexander A. Tarnutzer, D. I. Chang |
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| Přispěvatelé: | University of Zurich, Tarnutzer, A A |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
10018 Ophthalmology Clinic
Adult Male pathology [Spinocerebellar Ataxias] Pathology medicine.medical_specialty Ataxia genetics [Phospholipases] Hereditary spastic paraplegia physiopathology [Spinocerebellar Ataxias] Medizin genetics [Hypogonadism] 610 Medicine & health PNPLA6 protein human physiopathology [Hypogonadism] Atrophy physiopathology [Retinal Dystrophies] Hypogonadotropic hypogonadism pathology [Retinal Dystrophies] Retinal Dystrophies medicine Cerebellar Degeneration Humans Spinocerebellar Ataxias ddc:610 genetics [Spinocerebellar Ataxias] 10064 Neuroscience Center Zurich Boucher Neuhäuser syndrome Cerebellar ataxia business.industry Hypogonadism medicine.disease genetics [Retinal Dystrophies] 10040 Clinic for Neurology Pedigree 2728 Neurology (clinical) Neurology Phospholipases 10076 Center for Integrative Human Physiology 2808 Neurology Mutation Cerebellar vermis 570 Life sciences biology Neurology (clinical) medicine.symptom business pathology [Hypogonadism] Neuroscience |
| Zdroj: | Journal of neurology 262(1), 194-202 (2014). doi:10.1007/s00415-014-7555-9 |
| DOI: | 10.1007/s00415-014-7555-9 |
| Popis: | The combination of progressive cerebellar degeneration, hypogonadotropic hypogonadism and chorioretinal dystrophy defines the rare Boucher-Neuhäuser syndrome (BNS), which has recently been linked to autosomal-recessive mutations in the PNPLA6 gene in four index patients. Here we present two novel unrelated patients with BNS, where we identified four recessive PNPLA6 mutations (3 of them novel) as the genetic cause, using a targeted high-throughput approach. This finding provides the first replication from independent families that BNS is caused by PNPLA6 and, moreover, highlights PNPLA6 as the major gene leading to BNS. Given the fact that the major gene causing BNS has thus now been identified, we summarize the spectrum of clinical presentations and phenotype evolution of BNS based on a systematic in-depth review of the literature of previously published cases (n = 40). Both the two cases presented here and our review of the literature propose that the clinical presentation of BNS can be variable regarding both the age (ranging from 1 to 40 years) and the clinical symptoms at onset (cerebellar ataxia in 38 %; vision loss in 36 %; delayed puberty in 26 %). A substantial fraction of BNS cases may present with relatively selective atrophy of the superior and dorsal parts of the cerebellar vermis along with atrophy of the cerebellar hemispheres on MRI, while brainstem or cortical changes on MRI seem to be present only in small fractions. Also in the literature, no other major genetic causes of BNS other than PNPLA6 mutations were identified. |
| Databáze: | OpenAIRE |
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