White matter disorders and cerebral calcification - narrow panel

Gene: ERCC3

Red List (low evidence)

The rating of this gene has been updated to Red 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

Red List (low evidence)

Comment on list classification: Leaving rating as green, but with recommendation for red rating following GMS review. No evidence that variants in this gene is associated with white matter disease.

Created: 11 May 2021, 12:51 p.m. | Last Modified: 11 May 2021, 12:51 p.m.

Panel Version: 1.80

Associated with Trichothiodystrophy 2, photosensitive #616390 and Xeroderma pigmentosum, group B #610651 in OMIM.

Reviewed literature reporting cases associated with disease. No specific white matter abnormality phenotypes reported.

Trichothiodystrophy 2, Photosensitive
PMID: 9012405 - Weeda et al 1997 - report 2 siblings (TTD6VI and TTD4VI) with a mild Trichothiodystrophy phenotype and biallelic variants in ERRC3 (XPB). No white matter abnormalities noted. In PMID: 16947863 - Oh et al 2006 it is reported that they nave normal intelligence and neurological exam.

Xeroderma pigmentosum, group B
PMID: 2167179 - Weeda et al 1990 and PMID: 16947863 - Oh et al 2006 - report a patient (XP11BE) with Xeroderma pigmentosum and Cockayne's syndrome. Two variants in ERCC3 reported. No white matter abnormalities noted, but in Oh et al they note decreased nerve conduction velocity, enlarged cerebral ventricles, basal ganglia calcifications.

PMID: 8408834, 8304337 and 16947863 - report 2 brothers (XPCS1BA and XPCS2BA) with Cockayne syndrome and xeroderma pigmentosum and variants in ERCC3. PMID: 16947863 gives a description of the patients and list late onset of neurologic impairment,decreased nerve conduction velocity, demyelinating neuropathy, and enlarged cerebral ventricles among the features.

PMID: 16947863 - Oh et al 2006 - report on variants in previously identified patients but also two new patients (XP131MA and XP183MA) with severe XP/CS. Neurological features include decreased nerve conduction velocity, enlarged cerebral ventricles, cerebellar atrophy, and calcification of the basal ganglia in the first patient and progressive loss of mental development in the second.

Created: 11 May 2021, 12:50 p.m. | Last Modified: 11 May 2021, 12:50 p.m.

Panel Version: 1.79

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Trichothiodystrophy 2, photosensitive, OMIM:616390; Xeroderma pigmentosum, group B, OMIM:610651

Publications

• 9012405
• 2167179
• 16947863
• 8408834
• 8304337

Red List (low evidence)

White matter changes have been reported in Trichothiodystrophy cases, but no neurological findings have been reported for the subtype of the condition caused by ERCC3.

Created: 15 Sep 2020, 10:19 a.m. | Last Modified: 15 Sep 2020, 10:19 a.m.

Panel Version: 1.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Trichothiodystrophy 2, photosensitive 616390