Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome

Gene: RNF113A

Green List (high evidence)

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

Created: 31 Jan 2023, 4:31 p.m. | Last Modified: 31 Jan 2023, 4:31 p.m.

Panel Version: 2.27

Comment on list classification: Associated with relevant phenotype in OMIM (MIM# 300953) and as possible Gen2Phen gene for X-linked trichothiodystrophy. At least 3 terminating variants reported in unrelated cases. Supportive functional studies also reported. Upgraded from Red to Amber but this gene should be promoted to Green at the next review.

Created: 30 Sep 2021, 2:47 p.m. | Last Modified: 30 Sep 2021, 2:47 p.m.

Panel Version: 2.15

Green List (high evidence)

In 2016 the RNF113A gene was added to R227 as a red gene because it was a "Possible DD gene for X-LINKED TRICHOTHIODYSTROPHY, and one family report in OMIM".

The family reported in OMIM was found by Tarpey et al (2009) to have the following likely pathogenic variant, RNF113A c.901C>T p.(Gln301Ter). Corbett et al (2015) showed that the variant is associated with X-linked form of nonphotosensitive trichothiodystrophy (XL-TTD) that has the following clinical phenotype: profound intellectual disability, microcephaly, partial corpus callosum agenesis, microphallus, and absent or rudimentary testes. Functional studies showed that it altered DNA alklation. Since this family was reported, three other families with XL-TTD and RNF113A variants have been discovered. In 2020, Tessarech et al identified the same RNF113A c.901C>T p.(Gln301Ter) variant in two foetuses from the same family that had the same clinical phenotypes. Mendelsohn et al (2020) identified the following pathogenic variants in two unrelated males with XL-TTD: RNF113A c.903_910del p.(Gln302fs) and RNF113A c.897_898del p.(Cys299Ter). Shostak et al showed that RNF113A promotes cell survival upon DNA damage as a spliceosome subunit.. This is a total of 4 unrelated cases with the same XL-TTD clinical phenotype that have RNF113A variants which supports it being upgraded from a red to green gene.

Created: 13 Sep 2021, 2:31 p.m. | Last Modified: 13 Sep 2021, 2:31 p.m.

Panel Version: 2.9

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
X-linked nonphotosensitive trichothiodystrophy; intellectual disability; partial corpus callosum agenesis; microcephaly; microphallus; hypergonadotropic hypogonadism

Publications

• (PMID: 19377476): (PMID: 25612912): (PMID:31793730): (PMID 31880405): (PMID:32152280)

Comment on list classification: Possible DD gene for X-LINKED TRICHOTHIODYSTROPHY, and one family report in OMIM.

Created: 28 Nov 2016, 5:18 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
?Trichothiodystrophy 5, nonphotosensitive