Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: MSX2
Green- for recurrent mutation only (P148L/P148H). AD. Blueprint genetics note that the gene is at least partially duplicated elsewhere in the genome. Fs/LOF associated with enlarged parietal foramina. Note added by GOSH: Pseudogene MSX2P1 ; Review on behalf of Tracy Lester/Andrew Wilkie/GOSHCreated: 5 Mar 2019, 11:33 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Craniosynostosis, type 2, 604757; Parietal foramina 1, 168500; Parietal foramina with cleidocranial dysplasia, 168550; Craniosynostosis; MSX2-related craniosynostosis
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: MSX2; Suggested initial gene rating: greenCreated: 5 Mar 2019, 11:21 a.m.
Comment on list classification: Current diagnosticCreated: 1 Feb 2016, 10:13 a.m.
Only missense mutations at p.Pro148, and whole gene duplications, associated with craniosynostosis. Heterozygous loss-of-function causes parietal foraminaCreated: 14 Sep 2015, 11:26 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
MSX2-related craniosynostosis
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Source NHS GMS was added to MSX2. Rating Changed from Green List (high evidence) to Green List (high evidence)
Phenotypes for MSX2 were set to Craniosynostosis, type 2, 604757; Parietal foramina 1, 168500; Parietal foramina with cleidocranial dysplasia, 168550; Craniosynostosis; MSX2-related craniosynostosis
Publications for MSX2 were set to 8106171; 23949913; 23918290
Mode of pathogenicity for MSX2 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
MSX2 was added to Craniosynostosis syndromespanel. Sources: Expert list
Model of inheritance for gene MSX2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
MSX2 was added to Craniosynostosis syndromespanel. Sources: Illumina TruGenome Clinical Sequencing Services
MSX2 was added to Craniosynostosis syndromespanel. Sources: Radboud University Medical Center, Nijmegen