Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: B3GAT3

Green List (high evidence)

Ritelli et al 2019 - Patient with 2 compound het likely pathogenic B3GAT3 variants. In table 2 they summarise the clinical features of all patients with B3GAT3 variants - patient reported in this paper yes (dolichocephaly), also reported in all patients from refs 1,2 & 6 and 3/7 patients from refs 4,7 & 8. They summarise in table 3 that in the clinical feuatures assoc with linkeropathies, craniosynostosis was reported in 12/15 cases (although 25 is total number of cases so presumably nothing mentioned in the other 10).

Created: 22 Jan 2021, 3:51 p.m. | Last Modified: 22 Jan 2021, 3:51 p.m.

Panel Version: 2.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
craniosynostosis MIM245600

Publications

• 31438591

Green List (high evidence)

Craniosynostosis is a feature of B3GAT3-related joint dislocations. Reported in multiple unrelated individuals and summarised in PMID 31438591 (2019)

Created: 2 Jul 2020, 10:36 a.m. | Last Modified: 2 Jul 2020, 10:36 a.m.

Panel Version: 2.9

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects, MIM# 245600

Publications

• 31438591

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Yauy Genet Med 20:269 (2018) 6 patients from 4 unrelated families homozygous for c.667G>A (p.Gly223Ser) ; Review on behalf of Tracy Lester/Andrew Wilkie

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Craniosynostosis and bone fragility

Publications

• Yauy Genet Med 20:269 (2018)

I don't know

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 5 Mar 2022, 5:41 p.m. | Last Modified: 5 Mar 2022, 5:41 p.m.

Panel Version: 2.63

Comment on list classification: Leaving the rating as amber for now, but with recommendation for green rating following GMS review. 3 independent cases with dolichocephaly/craniosynostosis reported and variants in B3GAT3. Cases from Morocco and India have a c.667G>A (p.Gly223Ser) variant but Ritelli et al 2019 reports an additional case with two different compound het variants.

Created: 26 Jan 2021, 4:16 p.m. | Last Modified: 26 Jan 2021, 4:16 p.m.

Panel Version: 2.20

As reported by 2 expert reviewers, PMID:31438591 (Ritelli et al 2019) report a further case of a patient with compound het missense changes (c.481C>T, p.(Arg161Trp) and c.889C>T (p.(Arg297Trp)) in B3GAT3 and a clinical presentation suggestive of spondylodysplastic Ehlers-Danlos syndrome which includes dolichocephaly. In Table 2 the paper lists the clinical features of all patients with B3GAT3 variants reported to date, however, some of these patients appear to have variants in AEBP1 (ENSG00000106624) rather than B3GAT3 (ENSG00000149541) e.g. PMID: 29606302 (reference 2 in the table).

PMID: 31196143 - Colman et al 2019 - report an Indian boy with complex linkeropathy and phenotypic features that include dolichocephaly. He was found to have a homozygous variant in B3GAT3 (c.667G > A, p.(Gly223Ser)) that was previously reported by Yauy et al. Another patient with a B3GAT3 variant is reported but dolichocephaly is not noted.

Created: 26 Jan 2021, 4:10 p.m. | Last Modified: 26 Jan 2021, 4:10 p.m.

Panel Version: 2.19

Comment on list classification: Upgrading from red to amber. Amber rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. The group decided to rate amber until there is more evidence for the gene-disease association.

Created: 21 May 2019, 4:09 p.m.

PMID: 28771243 - Yauy et al 2018 - six patients from four unrelated consanguineous families, all from Morocco. All sequenced patients showed a unique homozygous mutation of c.667G >A, p.Gly223Ser in the B3GAT3 gene. 3 patients from 2 families showed craniosynostosis.

Created: 14 May 2019, 12:27 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: B3GAT3; Suggested initial gene rating: green

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