Prevalence of RFC1-Mediated Spinocerebellar Ataxia in a United States Ataxia Cohort
| Autor: | Brent L. Fogel, Giacomo Glotzer, Christopher M. Gomez, Susan Perlman, Vikram Khurana, Yuanming Mao, Paul J. Lockhart, Darice Wong, Dona Aboud Syriani, Claudio M. de Gusmao, Soma Das, Sharon Hassin-Baer, Sameer Andani |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Vestibular areflexia medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Ataxia Cerebellar ataxia business.industry 030305 genetics & heredity medicine.disease RFC1 3. Good health 03 medical and health sciences 0302 clinical medicine Internal medicine Cohort Spinocerebellar ataxia Medicine medicine.symptom Allele business Trinucleotide repeat expansion 030217 neurology & neurosurgery |
| DOI: | 10.1101/790006 |
| Popis: | ObjectiveRepeat expansions in RFC1 and DAB1 have recently been identified as causing cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) and spinocerebellar ataxia 37 (SCA37), respectively. We evaluated the prevalence of these repeat-expansions in an undiagnosed ataxia cohort from the United States.MethodsA cohort of 596 patients with undiagnosed familial or sporadic cerebellar ataxia were evaluated at a tertiary referral ataxia center and excluded for common genetic causes of cerebellar ataxia. Patients were then screened for the presence of pathogenic repeat expansions in RFC1 (AAGGG) and DAB1 (ATTTC) using fluorescent repeat primed polymerase chain reaction (RP-PCR). Two additional undiagnosed ataxia cohorts from different centers, totaling 96 and 13 patients respectively, were subsequently screened for RFC1 resulting in a combined 705 subjects tested.ResultsIn the initial cohort, 42 samples were identified with one expanded allele in the RFC1 gene (7.0%), and 9 had two expanded alleles (1.5%). For the additional cohorts, we found 12 heterozygous samples (12.5%) and 7 biallelic samples (7.3%) in the larger cohort, and 1 heterozygous sample (7.7%) and 3 biallelic samples (23%) in the second. In total, 19 patients were identified with biallelic repeat expansions in RFC1 (2.7%). Of these 19 patients, 6 (32%) had a clinical diagnosis of CANVAS, 10 had cerebellar ataxia with neuropathy (53%), and 3 had spinocerebellar ataxia (16%). No patients were identified with expansions in the DAB1 gene.ConclusionIn a large undiagnosed ataxia cohort from the United States, biallelic pathogenic repeat expansion in RFC1 was observed in 2.7%. Testing should be strongly considered in ataxia patients, especially those with CANVAS or neuropathy. |
| Databáze: | OpenAIRE |
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