Publication
A new variant in the NALCN channel is responsible for cerebellar ataxia and cognitive impairment
| dc.contributor.author | Cabrita Pinto, Rute Luísa | |
| dc.contributor.author | Fancellu, Roberto | |
| dc.contributor.author | Markushi, Tiziana Benzi | |
| dc.contributor.author | Viaggi, Silvia | |
| dc.contributor.author | Testa, Barbara | |
| dc.contributor.author | Conteduca, Giuseppina | |
| dc.contributor.author | Fitzsimmons, Lane | |
| dc.contributor.author | Coviello, Domenico | |
| dc.contributor.author | Covone, Angela Elvira | |
| dc.date.accessioned | 2026-01-05T11:27:57Z | |
| dc.date.available | 2026-01-05T11:27:57Z | |
| dc.date.issued | 2025-10-11 | |
| dc.description.abstract | CLIFAHDD syndrome (OMIM # 616266) is a rare neurodevelopmental disorder caused by mutations in the NALCN gene. It is characterized by hypotonia, developmental delay, and congenital contractures of the limbs and face. We report a 33-year-old Italian woman with a mild form of CLIFAHDD who exhibited early-onset language difficulties and mild intellectual disability and later developed gait and balance impairments in adulthood. Whole Exome Sequencing (WES) identified a novel missense variant c.1514A>T; p.(Lys505Met) in the NALCN gene. The allele frequency of this variant is not detected (MAF = 0.0), the variant is classified as likely pathogenic according to ACMG criteria, and predicted to be probably damaging by PolyPhen-2. It affects a critical residue within the second pore-forming domain of the NALCN channel, potentially altering lipid interactions and channel regulation. Sanger sequencing and segregation analysis confirmed the variant to be heterozygous and de novo. The patient's milder symptoms and later onset, compared to severe pediatric cases, suggest that the clinical spectrum of CLIFAHDD syndrome may be broader than previously recognized. These findings underscore the potential influence of mutation location on disease presentation and severity. | eng |
| dc.identifier.doi | 10.3390/genes16101181 | |
| dc.identifier.other | 41153398 | |
| dc.identifier.uri | http://hdl.handle.net/10400.1/28055 | |
| dc.language.iso | eng | |
| dc.peerreviewed | yes | |
| dc.publisher | MDPI | |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject | CLIFAHDD syndrome | |
| dc.subject | NALCN | |
| dc.subject | Whole Exome Sequencing | |
| dc.subject | Neurodevelopmental disorders | |
| dc.subject | Sodium channels | |
| dc.title | A new variant in the NALCN channel is responsible for cerebellar ataxia and cognitive impairment | eng |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.issue | 10 | |
| oaire.citation.startPage | 1181 | |
| oaire.citation.title | Genes | |
| oaire.citation.volume | 16 | |
| oaire.version | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |
| person.familyName | Cabrita Pinto | |
| person.givenName | Rute Luísa | |
| person.identifier | 2785254 | |
| person.identifier.ciencia-id | 221A-6F43-797D | |
| person.identifier.orcid | 0000-0001-8192-5803 | |
| relation.isAuthorOfPublication | 45652543-7c85-4f89-8386-33dd983099c1 | |
| relation.isAuthorOfPublication.latestForDiscovery | 45652543-7c85-4f89-8386-33dd983099c1 |