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Mendeliome v1.3486 SSPO Sarah Milton changed review comment from: The HGNC approved symbol for this gene is SSPOP which refers to SCO-spondin pseudogene. Recently, it has been demonstrated this gene produces a functional protein; subcommissural organ-spondin, which plays a role in neural development and function. Given the previous pseudogene status most annotation will include n. as opposed to c. numbers (including in gnomAD v4).

PMID: 41077560 describes 4 individuals from 3 families with biallelic variants in SSPOP with a neurodevelopmental disorder. Phenotype is encompassed by epilepsy (onset <2 years old), developmental delay, autism and behavioural issues.
Variant types include missense, frameshift and splice site.

No homozygous nonsense/frameshift variants in gnomad v4. (some hom splice site).

Supportive functional studies including zebrafish knockout with epileptiform activity. Mouse knockout demonstrated reduced reissner’s fibre formation/smaller brain ventricles/spinal curvature anomalies.

It was noted by authors another publication PMID: 32028786 discussed 2 related individuals - a grandmother and grandchild with homozygous frameshift variants in SSPOP (exact variant not provided) who both were just documented to have cervical cleft, no mention of ID/epilepsy.
Sources: Literature; to: The HGNC approved symbol for this gene is SSPOP which refers to SCO-spondin pseudogene. Recently, it has been demonstrated this gene produces a functional protein; subcommissural organ-spondin, which is a large secreted glycoprotein that plays a role in neural development and function. Given the previous pseudogene status most annotation will include n. as opposed to c. numbers (including in gnomAD v4).

PMID: 41077560 describes 4 individuals from 3 families with biallelic variants in SSPOP with a neurodevelopmental disorder. Phenotype is encompassed by epilepsy (onset <2 years old), developmental delay, autism and behavioural issues.
Variant types include missense, frameshift and splice site.

No homozygous nonsense/frameshift variants in gnomad v4. (some hom splice site).

Supportive functional studies including zebrafish knockout with epileptiform activity. Mouse knockout demonstrated reduced reissner’s fibre formation/smaller brain ventricles/spinal curvature anomalies.

It was noted by authors another publication PMID: 32028786 discussed 2 related individuals - a grandmother and grandchild with homozygous frameshift variants in SSPOP (exact variant not provided) who both were just documented to have cervical cleft, no mention of ID/epilepsy.
Sources: Literature
Mendeliome v1.3486 SSPO Sarah Milton gene: SSPO was added
gene: SSPO was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: SSPO.
Mode of inheritance for gene: SSPO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SSPO were set to PMID: 41077560
Phenotypes for gene: SSPO were set to Neurodevelopmental disorder, MONDO:0700092, SSPOP-related
Review for gene: SSPO was set to GREEN
Added comment: The HGNC approved symbol for this gene is SSPOP which refers to SCO-spondin pseudogene. Recently, it has been demonstrated this gene produces a functional protein; subcommissural organ-spondin, which plays a role in neural development and function. Given the previous pseudogene status most annotation will include n. as opposed to c. numbers (including in gnomAD v4).

PMID: 41077560 describes 4 individuals from 3 families with biallelic variants in SSPOP with a neurodevelopmental disorder. Phenotype is encompassed by epilepsy (onset <2 years old), developmental delay, autism and behavioural issues.
Variant types include missense, frameshift and splice site.

No homozygous nonsense/frameshift variants in gnomad v4. (some hom splice site).

Supportive functional studies including zebrafish knockout with epileptiform activity. Mouse knockout demonstrated reduced reissner’s fibre formation/smaller brain ventricles/spinal curvature anomalies.

It was noted by authors another publication PMID: 32028786 discussed 2 related individuals - a grandmother and grandchild with homozygous frameshift variants in SSPOP (exact variant not provided) who both were just documented to have cervical cleft, no mention of ID/epilepsy.
Sources: Literature
Mendeliome v1.2861 SPOP Zornitza Stark Phenotypes for gene: SPOP were changed from Intellectual disability; dysmorphism; microcephaly; macrocephaly to Nabais Sa-de Vries syndrome, type 1 MIM#618828; Nabais Sa-de Vries syndrome, type 2, MIM#618829
Mendeliome v1.2860 SPOP Zornitza Stark edited their review of gene: SPOP: Changed phenotypes: Nabais Sa-de Vries syndrome, type 1 MIM#618828, Nabais Sa-de Vries syndrome, type 2, MIM#618829
Mendeliome v0.1563 SPOP Zornitza Stark Marked gene: SPOP as ready
Mendeliome v0.1563 SPOP Zornitza Stark Gene: spop has been classified as Green List (High Evidence).
Mendeliome v0.1563 SPOP Zornitza Stark Classified gene: SPOP as Green List (high evidence)
Mendeliome v0.1563 SPOP Zornitza Stark Gene: spop has been classified as Green List (High Evidence).
Mendeliome v0.1562 SPOP Zornitza Stark gene: SPOP was added
gene: SPOP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPOP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPOP were set to 32109420
Phenotypes for gene: SPOP were set to Intellectual disability; dysmorphism; microcephaly; macrocephaly
Mode of pathogenicity for gene: SPOP was set to Other
Review for gene: SPOP was set to GREEN
Added comment: Seven individuals reported with de novo missense variants in this gene. Gain-of-function variants associated with microcephaly whereas dominant-negative variants associated with macrocephaly.
Sources: Literature