Skeletal dysplasiaGene: PISD
Comment on list classification: There is enough evidence for this gene to be rated GREEN on the next major review - at least five unrelated families (three with the same founder variant) presenting skeletal dysplasia associated with biallelic variants in this gene.
Created: 19 Aug 2020, 2:31 p.m. | Last Modified: 19 Aug 2020, 2:31 p.m.
Panel Version: 2.13
Associated with Liberfarb syndrome in OMIM, but not in G2P.
PMID: 31263216 (2019) - In two sets of brothers from unrelated consanguineous families, sequencing revealed homozygosity for a 10-bp deletion (c.904-12_904-3delCTATCACCAC) in the PISD gene. The patients presented with Liberfarb syndrome, characterised by skeletal dysplasia, short stature, early-onset retinal degeneration, developmental delay, microcephaly, and hearing loss. Authors noted phenotypic overlap with another previously described case (PMID: 3561949 (1986)), prompting follow-up investigation using paraffin-embedded tissue which yielded an identical homozygous variant. Haplotype analysis indicated a founder effect between all five individuals.
PMID: 30858161 (2019) - Two sisters with progressive short stature, skeletal dysplasia, white matter abnormalities, congenital cataracts, sensorineural hearing loss, and mild global developmental delay, associated with compound heterozygous variants (c.830G>A and c.697+5G>A) in the PISD gene.
PMID: 30488656 (2019) - Two unrelated individuals with an 'unclassifiable' form of spondyloepimetaphyseal dysplasia, as well as short stature, microcephaly, mild facial dysmorphism. Vision, hearing, and psychomotor development were reported to be normal for both patients. WES identified the same homozygous missense variant (c.797G>A) in PISD in both patients. Analysis revealed a common haplotype, which indicated remote consanguinity. Supporting functional data using patient-derived fibroblasts.
Created: 19 Aug 2020, 2:26 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Liberfarb syndrome, 618889
Gene: pisd has been classified as Amber List (Moderate Evidence).
gene: PISD was added gene: PISD was added to Skeletal dysplasia. Sources: Literature for-review tags were added to gene: PISD. Mode of inheritance for gene: PISD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PISD were set to 31263216; 30858161; 30488656; 3561949 Phenotypes for gene: PISD were set to Liberfarb syndrome, 618889 Review for gene: PISD was set to GREEN