Skeletal dysplasia
Gene: PUF60
>3 cases with variants in the gene, also deletions of 8q24.3. Verheij syndrome is characterized by growth retardation, delayed psychomotor development, dysmorphic facial features, and skeletal, mainly vertebral, abnormalities. ; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Verheij syndrome, 615583; VRJS
Publications
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: PUF60; Initial rating suggestion: green if SDCreated: 6 Mar 2019, 11:36 a.m.
Comment on list classification: changed from red to green due to recent paper and internal clinical reviewCreated: 31 Oct 2017, 4:16 p.m.
Confirmed gene in Developmental Disorders Genotype-Phenotype Database (DDG2P) for PUF60 syndrome. Recent papers 28327570 (2017), 27804958 (2016) give evidence for ID not yet captured in OMIM/current diagnostics. Initially just classed as a micodeletion but subseqent recent papers have pinpointed PUF60 variants so there is enough evidence for LOF in PUF60 itself. In 2013, patients with microdeletions of chromosome 8q24.3 including PUF60 were found to have developmental delay, microcephaly, craniofacial, renal and cardiac defects (PMID: 24140112). In 2017 (PMID: 28327570) very similar phenotypes have been described in six patients with variants in PUF60, suggesting that it underlies the syndrome and they reported 12 additional patients with PUF60 variants, all patients had de novo heterozygous PUF60 variants on exome analysis, each confirmed by Sanger sequencing - four frameshift variants resulting in premature stop codons, three missense variants that clustered within the RNA recognition motif of PUF60 and five essential splice-site (ESS) variant. The consistent feature was developmental delay and most patients had short stature. Heterozygote loss-of-function variants in PUF60 caused a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function. Added microdeletion tag, as this might be important in relation to CNV calls.Created: 31 Oct 2017, 4:13 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Verheij syndrome, 615583; VRJS; Chromosome 8q24.3 deletion syndrome; PUF60 syndrome
Publications
Added phenotypes Verheij syndrome, 615583; VRJS for gene: PUF60 Publications for gene PUF60 were changed from 28327570; 27804958; 24140112 to 27804958; 28327570; 24140112
Source NHS GMS was added to PUF60. Rating Changed from Green List (high evidence) to Green List (high evidence)
This gene has been classified as Green List (High Evidence).
PUF60 was created by LouiseD
PUF60 was added to Unexplained skeletal dysplasiapanel. Sources: Other,Literature