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Severe microcephaly

Gene: PUF60

Green List (high evidence)

PUF60 (poly(U) binding splicing factor 60)
EnsemblGeneIds (GRCh38): ENSG00000179950
EnsemblGeneIds (GRCh37): ENSG00000179950
OMIM: 604819, Gene2Phenotype
PUF60 is in 10 panels

3 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 10 Mar 2022, 1:37 p.m. | Last Modified: 10 Mar 2022, 1:37 p.m.
Panel Version: 2.292

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting from grey to amber but with a recommendation for green rating at the next GMS review. 3 cases reported with heterozygous variants in PUF60 and a severe microcephaly phenotype.
Created: 19 May 2021, 3:51 p.m. | Last Modified: 19 May 2021, 3:51 p.m.
Panel Version: 2.176
Associated with Verheij syndrome #615583 (AD) in OMIM with microcephaly listed as a clinical feature.

23 patients with heterozygous variants in PUF60 reported, 3 with severe microcephaly.

PMID: 24140112 - Dauber et al 2013 - report a 21 year old female with a de novo heterozygous variant in PUF60 (c.505C>T;p.His169Tyr) with developmental delay, microcephaly, and craniofacial and cardiac defects. At age 20 her head circumference was −4.1 SD. They also report 5 individuals with 8q24.3 deletions that cover PUF60 and 2 other genes. Microcephaly reported in 3, but not in the severe range.

PMID: 27804958 - El Chehadeh et al 2017 - report 5 unrelated patients with de novo heterozygous protein altering variants in PUF60 found by WES. Only one had a microcephaly phenotype but this was severe (−3.2 SD at age 3 weeks)

PMID: 28327570- Low et al 2017 - report 12 patients with VRJS who had de novo heterozygous variants in PUF60 found by WES. Microcephaly was noted in 5 patients who had the following Z-scores (−2.48, −4.22, −2.09, −2.99, −2.53 respectively). Using a Z-score of -3 as the cut-off for severe microcephaly, this means one of the patients falls into this category and another one very close.

PMID: 28074499 - Santos-Simarro et al. 2017 - report 3 further patients with de novo heterozygous variants in PUF60 and a phenotype that includes developmental delay and growth retardation but no severe microcephaly reported.

PMID: 28471317 - Graziano et al 2018 - report a boy with a de novo heterozygous missense variant in PUF60 (same variant as reported by Santos-Simaro) who has a complex eye development and multisystem phenotype. Microcephaly is not reported.

PMID: 32851780 - Yamada et al 2020 - report a girl with a mild phenotype that does not include microcephaly and a de novo heterozygous frameshift variant in PUF60 leading to the addition of 21 extra amino acids at the carboxy end of the protein
Created: 19 May 2021, 3:50 p.m. | Last Modified: 19 May 2021, 3:50 p.m.
Panel Version: 2.173

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Verheij syndrome, OMIM:615583

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Over 15 affected individuals reported. Short stature and dev delay are consistent features. 5/12 in the largest case series had microcephaly in relation to stature (Z-scores −2.48, −4.22, −2.09, −2.99, −2.53 respectively).
Sources: Expert list
Created: 3 Sep 2020, 3:30 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Verheij syndrome, MIM# 615583

Publications

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
Phenotypes
  • Verheij syndrome, OMIM:615583
OMIM
604819
Clinvar variants
Variants in PUF60
Penetrance
None
Publications
Panels with this gene

History Filter Activity

10 Mar 2022, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating was removed from gene: PUF60.

10 Mar 2022, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source Expert Review Green was added to PUF60. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

19 May 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: puf60 has been classified as Amber List (Moderate Evidence).

19 May 2021, Gel status: 0

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: PUF60 were changed from Verheij syndrome, MIM# 615583 to Verheij syndrome, OMIM:615583

19 May 2021, Gel status: 0

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: PUF60 were set to 28327570

19 May 2021, Gel status: 0

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: PUF60.

3 Sep 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: PUF60 was added gene: PUF60 was added to Severe microcephaly. Sources: Expert list Mode of inheritance for gene: PUF60 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PUF60 were set to 28327570 Phenotypes for gene: PUF60 were set to Verheij syndrome, MIM# 615583 Review for gene: PUF60 was set to GREEN gene: PUF60 was marked as current diagnostic