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Intellectual disability

Gene: PUS7

Green List (high evidence)

PUS7 (pseudouridylate synthase 7 (putative))
EnsemblGeneIds (GRCh38): ENSG00000091127
EnsemblGeneIds (GRCh37): ENSG00000091127
OMIM: 616261, Gene2Phenotype
PUS7 is in 3 panels

2 reviews

Catherine Snow (Genomics England)

Comment on list classification: Gene status was changed from to Green due to a expert review by Konstantinos Varvagiannis. Associated with phenotype in OMIM and not in Gen2Phen. ID and DD identified in sufficient unrelated cases for PUS7 to be rated green on the ID panel.
Created: 30 May 2019, 10:45 a.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID: 30778726 (2019 - Shaheen et al.) reports 3 additional individuals from 2 consanguineous families. ID was a feature in all three. Variants reported: NM_019042.3 c.1507G>T or p.(Asp503Tyr) and c.329_332delCTGA or p.(Thr110Argfs*4), each found in homozygous state in affected individuals. As a result, PUS7 can be considered for inclusion in the ID panel as green. (The PMID for the article by de Brouwer et al. was added).
Created: 24 Feb 2019, 5:57 p.m.
de Brouwer et al. (https://doi.org/10.1016/j.ajhg.2018.10.026) report on 6 individuals from 3 unrelated families homozygous for truncating variants in PUS7.

The common phenotype consisted of ID with speech delay, microcephaly, short stature as well as aggressive behavior.

One frameshift, one nonsense and one intragenic deletion affecting the penultimate exon of PUS7 were private respectively to each family. qPCR demonstrated reduction of mRNA levels for the two first variants, with absence of the normally sized protein upon Western blot for the first one.

The deletion, not identified due to its small size by aCGH, was found in the exome analysis and confirmed by MAQ. RT-PCR demonstrated the absence of the respective exon in mRNA. The deletion resulted in introduction of a stop codon in the last exon and mRNA expression levels were shown to be normal. Western blot demonstrated absence of a normally sized protein.

Functional studies demonstrated defective tRNA and mRNA pseudouridylation. Drosophila knockouts recapitulated the behavioral phenotype.

Biallelic mutations in PUS1 and PUS3 have been reported in individuals with intellectual disability (as well as some other features noted in PUS7-related disorder).

PUS7 is included in the gene panel for ID offered by Radboud UMC (among the principal authors of the study).

Therefore this gene can be considered for inclusion in this panel as green (rather than amber).
Sources: Literature
Created: 8 Dec 2018, 8:49 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; Microcephaly; Short stature; Behavioral abnormality

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review
  • Expert Review Green
  • Expert Review
Phenotypes
  • Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature, 618342
  • Short stature
  • Microcephaly
  • Intellectual disability
  • Behavioral abnormality
OMIM
616261
Clinvar variants
Variants in PUS7
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

25 Jul 2019, Gel status: 3

Added New Source, Added New Source, Set Phenotypes, Set publications, Status Update

Catherine Snow (Genomics England)

Source Expert Review Green was added to PUS7. Source Expert Review was added to PUS7. Added phenotypes Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature, 618342 for gene: PUS7 Publications for gene PUS7 were changed from to 30778726; 30526862 Rating Changed from No List (delete) to Green List (high evidence)

8 Dec 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: PUS7 was added gene: PUS7 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: PUS7 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PUS7 were set to Intellectual disability; Microcephaly; Short stature; Behavioral abnormality Penetrance for gene: PUS7 were set to Complete Review for gene: PUS7 was set to GREEN gene: PUS7 was marked as current diagnostic