Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: SCARF2

Red List (low evidence)

An RNA-sequencing analysis on a cohort of patients with single suture craniosynostosis
identified four variants in SCARF2 (PMID:29168297):
1. c.1638G>T; p.Trp546Cys: no parental samples available, allele frequency = 4.60e-5 gnomAD v.2.1.1.
2. c.1688T>G; p.Val563Gly: de novo and absent from gnomAD.
3. c.1999A>C; p.Lys667Gln: maternally inherited, absent from gnomAD.
4. c.2593dupG; p.Ala865Serfs*184: paternally inherited, absent from gnomAD.

The significance of the heterozygous variants is not clear as only one is de novo.

A homozygous variant was reported as pathogenic for Van den Ende-Gupta syndrome: c.190T>C; p.Cys64Arg (PMID:29620724).

As there is only one variant reported each for de novo and homozygous states, the gene is rated red.

Created: 23 Jul 2023, 8:25 p.m. | Last Modified: 23 Jul 2023, 8:25 p.m.

Panel Version: 4.170

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Van den Ende-Gupta syndrome, OMIM:600920; craniosynostosis, MONDO:0015469

Publications

• 29168297
• 29620724
• 36980886

I don't know

2 brothers with CSS reported by Patel et al 2013. CSS also reported in a casewith a microdel involving SCARF2 (Molinatto et al 2011). Clarke et al 2017 show sig increase in damaging variant is SCARF2 in patients with single suture CSS. ; Review on behalf of Tracy Lester and Andrew Wilkie

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Van den Ende-Gupta syndrome

I don't know

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: SCARF2; Suggested initial gene rating: amber

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

Red List (low evidence)

Rare disorder comprising blepharophimosis, malar and/or maxillary hypoplasia, a narrow and beaked nose, everted lower lip, arachnodactyly, camptodactyly, peculiar skeletal abnormalities, and normal development and intelligence

Created: 15 Sep 2015, 9:20 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Van Den Ende-Gupta syndrome

Publications

• 20887961