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Cataracts

Gene: PISD

Red List (low evidence)

PISD (phosphatidylserine decarboxylase)
EnsemblGeneIds (GRCh38): ENSG00000241878
EnsemblGeneIds (GRCh37): ENSG00000241878
OMIM: 612770, Gene2Phenotype
PISD is in 3 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Rating Red, as cataracts (congenital) only reported in a single family with two affected sibs - additional cases required to ascertain the contribution of PISD variants to this phenotype.
Created: 19 Aug 2020, 2 p.m. | Last Modified: 19 Aug 2020, 3:06 p.m.
Panel Version: 2.9
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 early-onset retinal degeneration, skeletal dysplasia, short stature, developmental delay, microcephaly, and hearing loss. There was a concern for bilateral cataracts in one patient (patient 3), but a formal ophthalmological evaluation could not be performed. 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, 1:56 p.m. | Last Modified: 19 Aug 2020, 1:57 p.m.
Panel Version: 2.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Liberfarb syndrome, 618889

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

4 individuals in 2 unrelated but consanguineous families from Portugal and Brazil affected by early-onset retinal degeneration, sensorineural hearing loss, microcephaly, intellectual disability, and skeletal dysplasia with scoliosis and short stature (Liberfarb syndrome). Affected individuals shared a homozygous 10-bp deletion immediately upstream of the last exon of the PISD gene. In HEK293T cells, this variant led to aberrant splicing of PISD transcripts.

1 family with 2 sisters with congenital cataracts, short stature, and white matter changes identified compound heterozygous variants in the PISD gene. Decreased conversion of phosphatidylserine to PE in patient fibroblasts is consistent with impaired phosphatidylserine decarboxylase (PISD) enzyme activity.
Sources: Expert list
Created: 8 Jul 2020, 7:57 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; cataracts; retinal degeneration; microcephaly; deafness; short stature; white matter abnormalities

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
Phenotypes
  • Liberfarb syndrome, 618889
OMIM
612770
Clinvar variants
Variants in PISD
Penetrance
None
Publications
Panels with this gene

History Filter Activity

19 Aug 2020, Gel status: 1

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: PISD were set to 31263216; 30858161

19 Aug 2020, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: PISD were changed from Intellectual disability; cataracts; retinal degeneration; microcephaly; deafness; short stature; white matter abnormalities to Liberfarb syndrome, 618889

19 Aug 2020, Gel status: 1

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: pisd has been classified as Red List (Low Evidence).

8 Jul 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: PISD was added gene: PISD was added to Cataracts. Sources: Expert list Mode of inheritance for gene: PISD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PISD were set to 31263216; 30858161 Phenotypes for gene: PISD were set to Intellectual disability; cataracts; retinal degeneration; microcephaly; deafness; short stature; white matter abnormalities Review for gene: PISD was set to GREEN gene: PISD was marked as current diagnostic