Intellectual disability
Gene: RAD50

RAD50 (RAD50 double strand break repair protein)
EnsemblGeneIds (GRCh38): ENSG00000113522
EnsemblGeneIds (GRCh37): ENSG00000113522
OMIM: 604040, Gene2Phenotype
RAD50 is in 5 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

Red List (low evidence)

- PMID: 33378670 (2020) - single patient described with bone marrow failure, immunodeficiency and developmental defects, who was compound heterozygous for a frameshift and premature stop codon (c.2165dup; p.Glu723Glyfs∗5 - maternally inherited) and in-frame deletion (c.3109_3111del; p.Glu1035del - de novo) in the RAD50 gene.
Functional characterisation using patient-derived fibroblasts indicated defects in DNA replication, DNA repair, and DNA end resection; however, ATM-dependent DNA damage response remained intact. Studies in yeast modelling the variant corresponding to p.Glu1035del produced defects in both DNA repair and Tel1ATM-dependent signalling following thermal activation.

This is the third case published with biallelic variants in the RAD50 gene. Although authors report 'developmental defects', it is unclear whether this individual displayed cognitive impairment. Therefore, maintaining the Red gene rating on this panel.
Created: 1 Apr 2021, 3:19 p.m. | Last Modified: 1 Apr 2021, 3:19 p.m.

Panel Version: 3.990

Comment on list classification: Note uncertainty regarding ID in the first patient - PMID:1887849 states 'lack of mental retardation', while a later report PMID:19409520 describes 'mild to moderate retardation of psychomotor development'. ID was borderline in the second patient (at age 15 estimated IQ: 85).

Therefore, keeping rating Red awaiting further cases to clarify the relevance of ID to the phenotype associated with RAD50 variants.
Created: 21 Sep 2020, 3:01 p.m. | Last Modified: 21 Sep 2020, 3:34 p.m.

Panel Version: 3.330

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nijmegen breakage syndrome-like disorder, OMIM:613078

Publications

Created: 21 Sep 2020, 3:01 p.m.
Last Modified: 21 Sep 2020, 3:34 p.m.
Panel version: 3.990

Zornitza Stark (Australian Genomics)

I don't know

Second individual reported. Degree of ID unclear, probably in mild to moderate range.
Created: 8 Sep 2020, 10:53 p.m. | Last Modified: 8 Sep 2020, 10:53 p.m.

Panel Version: 3.295

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nijmegen breakage syndrome-like disorder, MIM# 613078

Publications

32212377

Created: 8 Sep 2020, 10:53 p.m.
Last Modified: 8 Sep 2020, 10:53 p.m.
Panel version: 3.295

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

Currently only one case described in the iterature with Nijmegen breakage syndrome-like disorder, noted with normal mental function (subsequent confusion in publications between retardation of psychomotor development and mental retardation)
Created: 18 Dec 2017, 3:39 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nijmegen breakage syndrome-like disorder,613078; NBSLD

Publications

Created: 18 Dec 2017, 3:39 p.m.

Panel version: Imported from Intellectual disability update Dec 2017 panel version 0.40

Caroline Wright (Sanger)

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
NIJMEGEN BREAKAGE SYNDROME-LIKE DISORDER

Publications

19409520

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Lu Raymond (university of cambridge )

Red List (low evidence)

Created: 23 Feb 2016, 11:07 a.m.

Panel version: 0.306

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Red

Phenotypes

Nijmegen breakage syndrome-like disorder, OMIM:613078

OMIM

604040

Clinvar variants

Variants in RAD50

Penetrance

Complete

Publications

Panels with this gene