White matter disorders and cerebral calcification - narrow panel

Gene: ERCC5

I don't know

The rating of this gene has been updated to Amber 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

I don't know

Comment on list classification: Leaving rating as green but with a recommendation for amber or red rating following GMS review. As Expert reviewer reports there is no specific white matter abnormalities/leukodystrphy reported in the cases to date.

Created: 11 May 2021, 3:45 p.m. | Last Modified: 11 May 2021, 3:45 p.m.

Panel Version: 1.88

Associated with Cerebrooculofacioskeletal syndrome 3 #616570 and Xeroderma pigmentosum, group G/Cockayne syndrome #278780 in OMIM.

ERCC5 is also known as XPG.

No predominant white matter disorder phenotype reported.

PubMed: 8818951 - Hamel et al. (1996)//9096355 - Nouspikel et al. (1997) - report a Moroccan boy with Cerebrooculofacioskeletal syndrome 3 and a biallelic variant in ERCC5. Cerebral MRI showed dysmyelination.

PubMed: 24700531 - Drury et al 2014 - report on five fetuses conceived to 3 sets of related first cousin parents presenting with abnormal ultrasound findings including contractures and microcephaly. The phenotype is consistent with Cerebrooculofacioskeletal syndrome 3. A biallelic variant in ERCC5 was found in the proband, and is heterozygous in each of the parents. MRI was carried out on one fetus and found no major abnormalities.

PMID: 11228268 - Zafeiriou et al 2002 - report an infant (XPCS4RO) with the very rare xeroderma pigmentosum group G (XP-G) with severe neurological involvement and features of Cockayne syndrome in which compound heterozygous variants (nonsense and missense) were found in ERCC5. Both computed tomography and brain magnetic resonance imaging demonstrated brain atrophy.

PMID: 8317483- Vermeulen et al. (1993) - 2 unrelated, severely affected patients (XPCS1LV and XPCS2LV) with the clinical characteristics of Cockayne sydrome in which ERCC5 variants were found by Nouspikel et al. (1997). In one nerve conduction velocity was normal, in the other nerve conduction velocity was decreased, and visual and auditory-evoked potentials were absent.

Created: 11 May 2021, 3:42 p.m. | Last Modified: 11 May 2021, 3:42 p.m.

Panel Version: 1.85

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebrooculofacioskeletal syndrome 3 OMIM:616570; Xeroderma pigmentosum, group G/Cockayne syndrome OMIM:278780

Publications

• 8818951
• 9096355
• 24700531
• 11228268
• 8317483

Red List (low evidence)

Cannot find specific reports of leukodystrphy/white matter changes associated with variants in this gene.

Created: 15 Sep 2020, 10:24 a.m. | Last Modified: 15 Sep 2020, 10:24 a.m.

Panel Version: 1.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebrooculofacioskeletal syndrome 3 616570; Xeroderma pigmentosum, group G 278780