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Severe microcephaly

Gene: PTPN23

Amber List (moderate evidence)

PTPN23 (protein tyrosine phosphatase, non-receptor type 23)
EnsemblGeneIds (GRCh38): ENSG00000076201
EnsemblGeneIds (GRCh37): ENSG00000076201
OMIM: 606584, Gene2Phenotype
PTPN23 is in 4 panels

2 reviews

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Promoting this gene from grey to amber, but with a recommendation for a green rating following GMS review. 1 confirmed case with severe microcephaly plus several further cases of microcephaly, not all of which have the degree of severity stated. Genomics England clinician confirms proposal for green rating.
Created: 30 Jun 2021, 11:18 a.m. | Last Modified: 30 Jun 2021, 11:18 a.m.
Panel Version: 2.209
Associated with Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity #618890 in OMIM,

Severe microcephaly (OFC > 3 SD below mean) confirmed in 1 case, a further 4 cases with microcephaly reported.

PMID:31395947 - Bend et al 2020 - 7 patients with biallelic variants in PTPN23. 2 have microcephaly noted (1 with occipito-frontal head circumference (OFC) −3SD along with severe growth restriction, in the other the degree is not noted). In a 3rd case borderline microcephaly is reported (10th percentile).

PMID:29899372 - Smigiel et al 2018 - 1 patient with severe developmental delay, epilepsy, cortical blindness, hypomyelination and brain atrophy and compound heterozygous PTPN23 variants (c.1902C>G;p.(Asn634Lys), c.2974delC;p.(Leu992Tyrfs*168) identified by WES. OFC at birth was 30 cm (2 cm below 3 percentile), weight 2320 g (300 g below 3 percentile), length 52 cm (50–90 percentile),

PMID: 29090338 - Sowada et al 2017- 1 patient with developmental and epileptic encephalopathy with compound heterozygous PTPN23 variants (c.3586C>T (p.Arg1196*) and c.1595C>T (p.Pro532Leu)). OFC at birth was 31 cm (− 2.6 SD) but weight was 50th and length 26th percentile.

PMID: 27848944 - Trujillano et al 2017 - 1 patient with homozygous c.904A>G p.(M302V) variant in PTPN23 and microcephaly reported as part of the clinical phenotype. No details as to severity of the microcephaly. They classify the variant as a VUS.

PMID: 25558065 - Alazami et al 2015 - 1 patient with a variant (NM_015466:c.3995G >
T:p.R1332L) in PTPN23 and Global developmental delay, epilepsy and brain atrophy. Microcephaly not mentioned in publication, however in Bend et al 2020 Table 1 says this patient has progressive microcephaly.
Created: 13 May 2021, 10:38 a.m. | Last Modified: 13 May 2021, 10:48 a.m.
Panel Version: 2.150

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, OMIM:618890

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Over 10 families reported with an autosomal recessive neurologic disorder characterised by global developmental delay apparent from early infancy, poor overall growth often with microcephaly (6/10), impaired intellectual development with delayed or absent speech, axial hypotonia, and peripheral spasticity. Additional common but variable features include early-onset seizures, optic atrophy with poor visual fixation, and dysmorphic facial features. Brain imaging shows cerebral atrophy, poor or absent myelination with loss of white matter volume, and often hypoplasia of the corpus callosum and/or cerebellum.
Sources: Expert list
Created: 3 Sep 2020, 3:22 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, OMIM:618890
Tags
Q2_21_rating
OMIM
606584
Clinvar variants
Variants in PTPN23
Penetrance
None
Publications
Panels with this gene

History Filter Activity

30 Jun 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: ptpn23 has been classified as Amber List (Moderate Evidence).

30 Jun 2021, Gel status: 0

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: PTPN23.

27 May 2021, Gel status: 0

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: PTPN23 were changed from Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890 to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, OMIM:618890

3 Sep 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: PTPN23 was added gene: PTPN23 was added to Severe microcephaly. Sources: Expert list Mode of inheritance for gene: PTPN23 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTPN23 were set to 31395947; 29899372; 29090338; 27848944; 25558065 Phenotypes for gene: PTPN23 were set to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890 Review for gene: PTPN23 was set to GREEN