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Genetic epilepsy syndromes

Gene: PSAP

Green List (high evidence)

PSAP (prosaposin)
EnsemblGeneIds (GRCh38): ENSG00000197746
EnsemblGeneIds (GRCh37): ENSG00000197746
OMIM: 176801, Gene2Phenotype
PSAP is in 12 panels

4 reviews

Rebecca Foulger (Genomics England curator)

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AR combined SAP deficiency. Harzer et al, 1989 & Schnabel et al, 2002 - first cousin parents - generalised clonic seizure shortly after birth - a second sib similarly aff - hom mutation identified. Hulkova et al, 2001 - fatal infantile storage disorder in a Slovakian infant - developed seizures and died age 3.5 months- hom mutation identified, IHC done. Kuchar et al, 2009 - male infant - developed treatment resistant clonic fits shortly after birth died at 55 days. Second patient - first generalised seizure at 43 months - patient 1 hom for a splicing variant and patient 2 compound het for a splice and a fs variant. Motta et al, 2016 - table 1 - 7 prev reported patients with PSAP defic - 4/7 say seizures. Both patients being reported by the paper have seizures as part of phenotype.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined SAP deficiency 611721; Gaucher disease, atypical 610539; Krabbe disease, atypical 611722; Metachromatic leukodystrophy due to SAP-b deficiency 249900

Publications

Eleanor Williams (Genomics England Curator)

Comment on list classification: Promoting to green after gaining access to PMID: 2514102 and confirming a second case of a patient showing seizures, which along with the mouse knockout model confirms the association with seizures. In addition there is a green expert review.
Created: 5 Dec 2018, 7:31 p.m.
Comment on phenotypes: Only added Combined SAP deficiency as a phenotype as evidence for seizures only found for this disorder.
Created: 5 Dec 2018, 5:18 p.m.
Comment on list classification: Keeping Amber rating, as only 1 confirmed case of a variant in PSAP in an individual with seizures. A mouse knockout model which does develop seizures also exists.
Created: 5 Dec 2018, 5:11 p.m.
A mouse SAP -/- knockout exists (PMID: 8776585) and surviving mice develop intermittent seizures and progress to continual tonic status epilepticus.
Created: 5 Dec 2018, 5:09 p.m.
Metachromatic leukodystrophy due to SAP-b deficiency
2 cases of children with variants in PSAP and saposin B deficiency have been reported in PMID: 8554069 (Henseler et al. 1996) and PMID: 10682309 (Wrobe et al. 2000). Neither child was reported to have seizures.
Created: 5 Dec 2018, 4:54 p.m.
Combined SAP deficiency
PMIDs: 2514102 (Harzer et al. 1989) and 1371116 (Schnabel et al. 1992) report 2 sibs with combined SAP deficiency with a homozygous mutation resulting in a M1L substitution. No precursor and no mature SAPs were detected in the patient's cells. Both parents were heterozygous for the mutation. The first child's clinical phenotype included generalized clonic seizure shortly after birth. The second pregnancy was terminated following diagnosis.

PMID: 11309366 (Hulkova et al. 2001) - In a Slovakian patient with fatal infantile combined SAP deficiency, a homozygous 1 bp deletion in the PSAP gene, inherited from both his parents . Immunohistochemical investigations indicated that saposins A, B, C, and D were all deficient. Generalized seizures developed within minutes of birth.
Created: 5 Dec 2018, 4:53 p.m.
Associated with Combined SAP deficiency and Metachromatic leukodystrophy due to SAP-b deficiency in OMIM both of which have seizures listed as part of their clinical phenotype. Not associated with either of these disorders in Gene2Phentoype.
Created: 5 Dec 2018, 4:53 p.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Seizures are part of the phenotype of these metabolic disorders.
Created: 19 Aug 2018, 11:49 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Metachromatic leukodystrophy due to SAP-b deficiency, MIM#249900; Combined SAP deficiency, MIM#611721

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

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to PSAP.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to PSAP.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: Seizures are part of the pheno

5 Dec 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: psap has been classified as Green List (High Evidence).

5 Dec 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: PSAP were changed from to Combined SAP deficiency 611721

5 Dec 2018, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: PSAP were set to

5 Dec 2018, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: PSAP was changed from to BIALLELIC, autosomal or pseudoautosomal

5 Dec 2018, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to PSAP. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

PSAP was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

PSAP was created by Sarah Leigh