Consolidation of the clinical and genetic definition of a
abnormalities
congenital
gene expression regulation
genetic variation
hereditary
neonatal diseases
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
07
12
2021
accepted:
13
01
2022
pubmed:
3
3
2022
medline:
26
10
2022
entrez:
2
3
2022
Statut:
ppublish
Résumé
A neurodevelopmental syndrome was recently reported in four patients with We newly identified 17 patients with All variants were novel, distinct and heterozygous. Seven HMG-domain missense and five stop-gain variants were classified as pathogenic or likely pathogenic variant (L/PV) as they precluded SOX4 transcriptional activity in vitro. Five HMG-domain and non-HMG-domain missense variants were classified as of uncertain significance (VUS) due to negative results from functional tests. When known, inheritance was de novo or from a mosaic unaffected or non-mosaic affected parent for patients with L/PV, and from a non-mosaic asymptomatic or affected parent for patients with VUS. All patients had neurodevelopmental, neurological and dysmorphic features, and at least one cardiovascular, ophthalmological, musculoskeletal or other somatic anomaly. Patients with L/PV were overall more affected than patients with VUS. They resembled patients with other neurodevelopmental diseases, including the These findings consolidate evidence of a fairly non-specific neurodevelopmental syndrome due to
Sections du résumé
BACKGROUND
A neurodevelopmental syndrome was recently reported in four patients with
METHODS
We newly identified 17 patients with
RESULTS
All variants were novel, distinct and heterozygous. Seven HMG-domain missense and five stop-gain variants were classified as pathogenic or likely pathogenic variant (L/PV) as they precluded SOX4 transcriptional activity in vitro. Five HMG-domain and non-HMG-domain missense variants were classified as of uncertain significance (VUS) due to negative results from functional tests. When known, inheritance was de novo or from a mosaic unaffected or non-mosaic affected parent for patients with L/PV, and from a non-mosaic asymptomatic or affected parent for patients with VUS. All patients had neurodevelopmental, neurological and dysmorphic features, and at least one cardiovascular, ophthalmological, musculoskeletal or other somatic anomaly. Patients with L/PV were overall more affected than patients with VUS. They resembled patients with other neurodevelopmental diseases, including the
CONCLUSION
These findings consolidate evidence of a fairly non-specific neurodevelopmental syndrome due to
Identifiants
pubmed: 35232796
pii: jmedgenet-2021-108375
doi: 10.1136/jmedgenet-2021-108375
pmc: PMC9433470
mid: NIHMS1774026
doi:
Substances chimiques
DNA
9007-49-2
SOX4 protein, human
0
SOXC Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1058-1068Subventions
Organisme : NINDS NIH HHS
ID : K08 NS105865
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR068308
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH074090
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH119705
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: AC and MJT are employees of GeneDx, Inc. Other authors have no competing interests.