Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies
Biallelic expansions of the AAGGG repeat in the replication factor C subunit 1 (RFC1) have recently been described to be responsible for cerebellar ataxia, peripheral neuropathy and vestibular areflexia syndrome. This genetic alteration has also allowed genetic classification in up to one-third of c...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2024
|
| _version_ | 1826314900833566720 |
|---|---|
| author | Nagy, S Carr, A Mroczek, M Rinaldi, S Curro, R Dominik, N Japzon, N Magrinelli, F Lunn, MP Manji, H Reilly, MM Cortese, A Houlden, H |
| author_facet | Nagy, S Carr, A Mroczek, M Rinaldi, S Curro, R Dominik, N Japzon, N Magrinelli, F Lunn, MP Manji, H Reilly, MM Cortese, A Houlden, H |
| author_sort | Nagy, S |
| collection | OXFORD |
| description | Biallelic expansions of the AAGGG repeat in the replication factor C subunit 1 (RFC1) have recently been described to be responsible for cerebellar ataxia, peripheral neuropathy and vestibular areflexia syndrome. This genetic alteration has also allowed genetic classification in up to one-third of cases with idiopathic sensory neuropathy. Here, we screened a well-characterized cohort of inflammatory neuropathy patients for RFC1 repeat expansions to explore whether RFC1 was increased from background rates and possibly involved in the pathogenesis of inflammatory neuropathy. A total of 259 individuals with inflammatory neuropathy and 243 healthy controls were screened for the AAGGG repeat expansion using short-range flanking PCR and repeat-primed PCR. Cases without amplifiable PCR product on flanking PCR and positive repeat-primed PCR were also tested for the mostly non-pathogenic expansions of the AAAGG and AAAAG repeat units. None of the patients showed biallelic AAGGG expansion of RFC1, and their carrier frequency for AAGGG was comparable with controls [n = 27 (5.2%) and n = 23 (4.7%), respectively; P > 0.5]. Data suggest that the pathologic expansions of AAGGG repeats do not contribute to the development of inflammatory neuropathies nor lead to misdiagnosed cases. Accordingly, routine genetic screening for RFC1 repeat expansion is not indicated in this patient population. |
| first_indexed | 2024-09-25T04:15:10Z |
| format | Journal article |
| id | oxford-uuid:3b028e4d-01b6-4ab5-ac8e-e242621f58d8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:14:47Z |
| publishDate | 2024 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:3b028e4d-01b6-4ab5-ac8e-e242621f58d82024-10-16T09:45:21ZPathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathiesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3b028e4d-01b6-4ab5-ac8e-e242621f58d8EnglishJisc Publications RouterOxford University Press2024Nagy, SCarr, AMroczek, MRinaldi, SCurro, RDominik, NJapzon, NMagrinelli, FLunn, MPManji, HReilly, MMCortese, AHoulden, HBiallelic expansions of the AAGGG repeat in the replication factor C subunit 1 (RFC1) have recently been described to be responsible for cerebellar ataxia, peripheral neuropathy and vestibular areflexia syndrome. This genetic alteration has also allowed genetic classification in up to one-third of cases with idiopathic sensory neuropathy. Here, we screened a well-characterized cohort of inflammatory neuropathy patients for RFC1 repeat expansions to explore whether RFC1 was increased from background rates and possibly involved in the pathogenesis of inflammatory neuropathy. A total of 259 individuals with inflammatory neuropathy and 243 healthy controls were screened for the AAGGG repeat expansion using short-range flanking PCR and repeat-primed PCR. Cases without amplifiable PCR product on flanking PCR and positive repeat-primed PCR were also tested for the mostly non-pathogenic expansions of the AAAGG and AAAAG repeat units. None of the patients showed biallelic AAGGG expansion of RFC1, and their carrier frequency for AAGGG was comparable with controls [n = 27 (5.2%) and n = 23 (4.7%), respectively; P > 0.5]. Data suggest that the pathologic expansions of AAGGG repeats do not contribute to the development of inflammatory neuropathies nor lead to misdiagnosed cases. Accordingly, routine genetic screening for RFC1 repeat expansion is not indicated in this patient population. |
| spellingShingle | Nagy, S Carr, A Mroczek, M Rinaldi, S Curro, R Dominik, N Japzon, N Magrinelli, F Lunn, MP Manji, H Reilly, MM Cortese, A Houlden, H Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies |
| title | Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies |
| title_full | Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies |
| title_fullStr | Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies |
| title_full_unstemmed | Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies |
| title_short | Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies |
| title_sort | pathologic rfc1 repeat expansions do not contribute to the development of inflammatory neuropathies |
| work_keys_str_mv | AT nagys pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT carra pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT mroczekm pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT rinaldis pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT curror pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT dominikn pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT japzonn pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT magrinellif pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT lunnmp pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT manjih pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT reillymm pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT cortesea pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies AT houldenh pathologicrfc1repeatexpansionsdonotcontributetothedevelopmentofinflammatoryneuropathies |