| Title: |
NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns |
| Authors: |
Stamberger, H.; Hammer, T.B.; Gardella, E.; Vlaskamp, D.R.M.; Bertelsen, B.; Mandelstam, S.; Lange, I. de; Zhang, J.; Myers, C.T.; Fenger, C.; Afawi, Z.; Fuerte, E.P. Almanza; Andrade, D.M.; Balcik, Y.; Zeev, B. Ben; Bennett, M.F.; Berkovic, S.F.; Isidor, B.; Bouman, A.; Brilstra, E.; Ø, L. Busk; Cairns, A.; Caumes, R.; Chatron, N.; Dale, R.C.; Geus, C. de; Edery, P.; Gill, D.; Granild-Jensen, J.B.; Gunderson, L.; Gunning, B.; Heimer, G.; Helle, J.R.; Hildebrand, M.S.; Hollingsworth, G.; Kharytonov, V.; Klee, E.W.; Koeleman, B.P.C.; Koolen, D.A.; Korff, C.; Küry, S.; Lesca, G.; Lev, D.; Leventer, R.J.; Mackay, M.T.; Macke, E.L.; McEntagart, M.; Mohammad, S.S.; Monin, P.; Montomoli, M.; Morava, E.; Moutton, S.; Muir, A.M.; Parrini, E.; Procopis, P.; Ranza, E.; Reed, L.; Reif, P.S.; Rosenow, F.; Rossi, M.; Sadleir, L.G.; Sadoway, T.; Schelhaas, H.J.; Schneider, A.L.; Shah, K.; Shalev, R.; Sisodiya, S.M.; Smol, T.; Stumpel, C.; Stuurman, K.; Symonds, J.D.; Mau-Them, F.T.; Verbeek, N.; Verhoeven, J.S.; Wallace, G.; Yosovich, K.; Zarate, Y.A.; Zerem, A.; Zuberi, S.M.; Guerrini, R.; Mefford, H.C.; Patel, C.; Zhang, Y.H.; Møller, R.S.; Scheffer, I.E. |
| Source: |
Genetics in Medicine; 363; 373; 1098-3600; 2; 23; ~Genetics in Medicine~363~373~~~1098-3600~2~23~~ |
| Publisher Information: |
2021 |
| Document Type: |
Electronic Resource |
| Abstract: |
Contains fulltext : 231688.pdf (Publisher’s version ) (Closed access); PURPOSE: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy. METHODS: Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy. RESULTS: Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism. CONCLUSION: NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic-atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants. |
| Availability: |
Open access content. Open access content |
| Other Numbers: |
NLQGE oai:repository.ubn.ru.nl:2066/231688; https://hdl.handle.net/2066/231688; https://doi.org/10.1038/s41436-020-00988-9; 1284049233 |
| Contributing Source: |
RADBOUD UNIVERSITEIT NAJMEGEN; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1284049233 |
| Database: |
OAIster |