White matter disorders and cerebral calcification - narrow panel

Gene: DCAF17

Green List (high evidence)

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

Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.

Panel Version: 2.9

Comment on list classification: Promoting this gene from grey to amber, but with a recommendation for green rating following GMS review. >3 cases of variants in DCAF17 in patients with Woodhouse-Sakati syndrome and white matter lesions observed in approx 70% of patients.

Created: 27 Apr 2021, 3:43 p.m. | Last Modified: 27 Apr 2021, 3:43 p.m.

Panel Version: 1.45

Associated with Woodhouse-Sakati syndrome in OMIM (#241080 (AR))
DCAF17 is also known as C2ORF37

PMID: 19026396 - Alazami et al 2008 - report single bp deletion in C2orf37 in 8 families of Saudi origin (identified as a founder mutation). Patients phenotypes included hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome (Woodhouse-Sakati syndrome). 3 other variants were then found in patients of different ethnicities (another 1 bp deletion leading to a frameshift and 2 variants affecting splice donor sites). The variants segregated with the disease in all families. The two 1 bp changes are predicted to affect the beta isoform only.

PMID: 20507343 - Alazami et al 2010 - report 7 new patients from 4 families (3 ethnic backgrounds, Italian, French Gypsy and Turkish) who present with Woodhouse-Sakati syndrome. Each family had a different variant in C2orf37 - 3 nonsense mutations and a splice site ablation.

PMID: 30409855 - Abusrair et al 2018 - reviewed brain MR images of 26 patients with a clinical and genetic diagnosis of Woodhouse-Sakati syndrome. All participants had confirmed homozygous pathogenic variants in DCAF17. White matter lesions were observed in 18 patients (69.2%).

PMID: 31726291 - Bohlega et al 2019 - report on 38 individuals from 17 families were identified as having a clinically and genetically confirmed diagnosis of WSS. All patients shared the same founder DCAF17: NM_001164821:exon4: c.436delC:p.L146fs frameshift deletion. Two groups identified based on phenotype. The age of onset of neurological symptoms for the group with the more severe phenotype was 12.6 ± 4.5 years (range, 9–17 years).

Created: 27 Apr 2021, 3:39 p.m. | Last Modified: 27 Apr 2021, 4:11 p.m.

Panel Version: 1.45

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Woodhouse-Sakati syndrome OMIM:241080

Publications

• 19026396
• 20507343
• 30409855

Green List (high evidence)

White matter changes are part of the phenotype.
Sources: Expert list

Created: 15 Sep 2020, 10:08 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Woodhouse-Sakati syndrome, MIM# 241080

Publications

• 19026396
• 20507343

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