Ocular coloboma

Gene: PUF60

Green List (high evidence)

Confirmed gene in Developmental Disorders Genotype-Phenotype Database (DDG2P) for PUF60 syndrome. Recent papers PMID:28327570 (2017) and PMID:27804958 (2016) give additional evidence 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: 1 Nov 2017, 11:15 a.m.

Comment on phenotypes: added phenotypes

Created: 1 Nov 2017, 11:12 a.m.

Comment on phenotypes: Verheij syndrome, 615583; VRJS; Chromosome 8q24.3 deletion syndrome; PUF60 syndrome; ocular abnormalities

Created: 1 Nov 2017, 11:12 a.m.

Comment on list classification: Additional cases for Verheij syndrome

Created: 1 Nov 2017, 11:11 a.m.

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

Phenotypes
Verheij syndrome, 615583; VRJS; Chromosome 8q24.3 deletion syndrome; PUF60 syndrome; ocular abnormalities

Publications

• 28327570
• 27804958
• 24140112

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
615583