Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: HUWE1

Green List (high evidence)

3 female cases with R110Q mutation have CSS (Moortgat et al 2018). Same variant also reported previously with similar phenotype. Also 2 males with R110W and CSS. Other variants cause ID only.

Created: 5 Mar 2019, 11:33 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
X-linked intellectual disability with CSS

I don't know

NOTE: Variants in a specific codon (R110) are associated with craniosynostosis. Variants in other codons are associated with intellectual disability.

Created: 21 May 2019, 12:35 p.m.

Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13.

Created: 21 May 2019, 12:33 p.m.

Comment on publications: Adding Moortgat et al 2018 PMID:29180823

Created: 2 May 2019, 4:09 p.m.

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: HUWE1; Suggested initial gene rating: green

Created: 5 Mar 2019, 11:21 a.m.

Green List (high evidence)

4 cases (2 male, 2 female) having craniosynostosis associated with mutation in identical codon p.Arg110; other mutations associated with X-linked intellectual disability. Mechanism of this genotype-phenotype specificity unknown but convincing regarding pathogenic link to mutations at this particular codon

Created: 11 Nov 2016, 12:23 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• 25985138
• 25590979