Further description of two individuals with de novo p.(Glu127Lys) missense variant in the ASCL1 gene.
ASCL1
Dysautonomia
Haddad syndrome
Hirschsprung disease
basic-helix-loop-helix domain
congenital central hypoventilation syndrome-1
neurocristopathies
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
29 Jan 2024
29 Jan 2024
Historique:
revised:
21
12
2023
received:
06
09
2023
accepted:
05
01
2024
medline:
30
1
2024
pubmed:
30
1
2024
entrez:
30
1
2024
Statut:
aheadofprint
Résumé
Achaete-Scute Family basic-helix-loop-helix (bHLH) Transcription Factor 1 (ASCL1) is a proneural transcription factor involved in neuron development in the central and peripheral nervous system. While initially suspected to contribute to congenital central hypoventilation syndrome-1 (CCHS) with or without Hirschsprung disease (HSCR) in three individuals, its implication was ruled out by the presence, in one of the individuals, of a Paired-like homeobox 2B (PHOX2B) heterozygous polyalanine expansion variant, known to cause CCHS. We report two additional unrelated individuals sharing the same sporadic ASCL1 p.(Glu127Lys) missense variant in the bHLH domain and a common phenotype with short-segment HSCR, signs of dysautonomia, and developmental delay. One has also mild CCHS without polyalanine expansion in PHOX2B, compatible with the diagnosis of Haddad syndrome. Furthermore, missense variants with homologous position in the same bHLH domain in other genes are known to cause human diseases. The description of additional individuals carrying the same variant and similar phenotype, as well as targeted functional studies, would be interesting to further evaluate the role of ASCL1 in neurocristopathies.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Bertrand N, Castro DS, Guillemot F. Proneural genes and the specification of neural cell types. Nat Rev Neurosci. 2002;3(7):517-530. doi:10.1038/nrn874
Hirsch MR, Tiveron MC, Guillemot F, Brunet JF, Goridis C. Control of noradrenergic differentiation and Phox2a expression by MASH1 in the central and peripheral nervous system. Development. 1998;125(4):599-608. doi:10.1242/dev.125.4.599
Parras CM, Schuurmans C, Scardigli R, Kim J, Anderson DJ, Guillemot F. Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity. Genes Dev. 2002;16(3):324-338. doi:10.1101/gad.940902
de Pontual L, Népote V, Attié-Bitach T, et al. Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse). Hum Mol Genet. 2003;12(23):3173-3180. doi:10.1093/hmg/ddg339
Weese-Mayer DE, Berry-Kravis EM, Ceccherini I, Keens TG, Loghmanee DA, Trang H. ATS congenital central hypoventilation syndrome subcommittee. An official ATS clinical policy statement: congenital central hypoventilation syndrome: genetic basis, diagnosis, and management. Am J Respir Crit Care Med. 2010;181(6):626-644. doi:10.1164/rccm.200807-1069ST
Broch A, Trang H, Montalva L, Berrebi D, Dauger S, Bonnard A. Congenital central hypoventilation syndrome and Hirschsprung disease: a retrospective review of the French National Registry Center on 33 cases. J Pediatr Surg. 2019;54(11):2325-2330. doi:10.1016/j.jpedsurg.2019.02.014
Lombardo RC, Porollo A, Cnota JF, Hopkin RJ. Congenital heart disease and aortic arch variants associated with mutation in PHOX2B. Genet Med. 2018;20(12):1538-1543. doi:10.1038/gim.2018.34
Amiel J, Sproat-Emison E, Garcia-Barcelo M, et al. Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 2008 Jan;45(1):1-14. doi:10.1136/jmg.2007.053959
Kim S, Twigg SRF, Scanlon VA, et al. Localized TWIST1 and TWIST2 basic domain substitutions cause four distinct human diseases that can be modeled in Caenorhabditis elegans. Hum Mol Genet. 2017;26(11):2118-2132. doi:10.1093/hmg/ddx107
Pattyn A, Goridis C, Brunet JF. Specification of the central noradrenergic phenotype by the homeobox gene Phox2b. Mol Cell Neurosci. 2000;15(3):235-243. doi:10.1006/mcne.1999.0826