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Genetic epilepsy syndromes

Gene: ALPL

Green List (high evidence)

ALPL (alkaline phosphatase, liver/bone/kidney)
EnsemblGeneIds (GRCh38): ENSG00000162551
EnsemblGeneIds (GRCh37): ENSG00000162551
OMIM: 171760, Gene2Phenotype
ALPL is in 10 panels

6 reviews

Helen Lord (Oxford Medical Genetics Laboratories)

Green List (high evidence)

AD and AR hypophosphatasia (HPP). Litmanovitz et al, 2002 (11999978) lethal perinatal HPP with two missense variants. Fukazawa et al 2018 (28802630) - newborn with infantile HPP and seizures - hom for a fs variant. Belachew et al, 2013 (23479201) 2 month old boy with infantile HPP and seizures - found to be a compound het for 2 diff fs variants. Guzel Nur et al, 2016 (27086862) - infantile HPP patient who presented with pyridoxine-responsive seizures - identified a novel hom del of 2 AA. Oyachi et al, 2018 (30083035) Newborn with HPP, seizures from day 2 - treated with drugs from day 4, compound het - missense and a fs variant, parents carriers, the fs variant has been observed previously and account for 40.9% of severe alleles in the Japanese population . Whyte et al, 2019 (30979546) retrospective study of a large cohort of paediatric patients with perinatal and infantile hypophosphatasia- vit B6 depend seizures seen in 10/38 cases (26%) - no genetic analysis done on these patients as far as i can tell. 100s of mutations listed on HGMD Pro in assocation with hypophosphatasia. All of these cases with epilepsy are AR, suggests that the AR conditionas are assoc with epilepsy not AD.
Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Alison Callaway (Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust)

Green List (high evidence)

Epilepsy can be associated with hypophosphatasia; no further literature identified. From reviews below, appears to have sufficient evidence for a green gene.
Created: 23 Aug 2019, 10:12 a.m. | Last Modified: 23 Aug 2019, 10:12 a.m.
Panel Version: 1.256

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

AR infantile hypophosphatasia and AR childhood phosphatasia assoc with epilepsy. Tenorio et al, 2017 - over 300 diff mutations in ALPL reported, disease severity variable and common clinical features are defects in bone and tooth mineralisation along with the biochemical hallmark of decreased serum alkaline phosphatase activity - no mention of seizures in any of the patient phenotypic information in this paper.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Hypophosphatasia, adult 146300; Hypophosphatasia, childhood 241510; Hypophosphatasia, infantile 241500; Odontohypophosphatasia, 146300;

Publications

Rebecca Foulger (Genomics England curator)

I don't know

Kept rating as Green based on post-Webex reviews from Helen Lord and Alison Callaway.
Created: 7 Sep 2019, 9:55 a.m. | Last Modified: 7 Sep 2019, 9:55 a.m.
Panel Version: 1.264
Comment on mode of inheritance: Updated Mode of Inheritance from 'BOTH monoallelic and biallelic' to 'BIALLELIC' based on Post-Webex review by Helen Lord: AR but not AD Hypophosphatasia is associated with seizures.
Created: 7 Sep 2019, 9:52 a.m. | Last Modified: 7 Sep 2019, 9:52 a.m.
Panel Version: 1.264
Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset that were re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
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: Amber.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
PMID:30979546: Whyte et al., 2019 report Vitamin B6-dependent seizures in 10/38 (26%) of patients: 7 patients had documented seizures and 3 patients had a family history of seizures based upon medical records.
Created: 22 Jul 2019, 11:16 a.m. | Last Modified: 27 Aug 2019, 10:18 a.m.
Panel Version: 1.258
PMID:30083035: Oyachi et al., 2018 report a newborn girl with compound het variants in ALPL (c.1559delT/p.Ser188Pro). The patient had seizures on days 2-4, treated with pyridoxine.
Created: 22 Jul 2019, 11:11 a.m. | Last Modified: 22 Jul 2019, 11:11 a.m.
Panel Version: 1.172
PMID:27086862 (2018) report a female infantile hypophosphatasia patient who presented with pyridoxine-responsive myoclonic seizures and a novel homozygous mutation in the ALPL gene(c.799_804delCACTTC). Parents were heterozygous for the variant.
Created: 22 Jul 2019, 11:11 a.m. | Last Modified: 22 Jul 2019, 11:11 a.m.
Panel Version: 1.172
Comment on publications: ALPL is called by its alias TNSALP in many publications.
Created: 9 Jul 2019, 8:06 p.m. | Last Modified: 9 Jul 2019, 8:06 p.m.
Panel Version: 1.147

Sarah Leigh (Genomics England Curator)

Comment on phenotypes: Hypophosphatasia, adult 146300 AD, AR;Hypophosphatasia, childhood 241510 AR;Hypophosphatasia, infantile 241500 AR;Odontohypophosphatasia 146300 AD, AR
Created: 17 Jul 2018, 9:37 a.m.
Comment on list classification: Based on review by Dr Arianna Tucci (Genomics England Clinical Fellow and Curator)
Created: 17 Jul 2018, 9:34 a.m.

Arianna Tucci (Genomics England Curator)

Green List (high evidence)

Associated with the phenotype in OMIM. seizures can be part of the phenotype. Note that seizures in are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine.
Created: 5 Jul 2018, 1 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Hypophosphatasia

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Hypophosphatasia, adult 146300 AD, AR
  • Hypophosphatasia, childhood 241510 AR
  • Hypophosphatasia, infantile 241500 AR
  • Odontohypophosphatasia 146300 AD, AR
Tags
drug-indication
OMIM
171760
Clinvar variants
Variants in ALPL
Penetrance
None
Publications
Panels with this gene

History Filter Activity

7 Sep 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: ALPL was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to ALPL.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to ALPL.

22 Jul 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: ALPL were set to 11999978; 28802630; 23479201; 27086862; 30655187; 30083035

22 Jul 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: ALPL were set to 11999978; 28802630; 23479201

9 Jul 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: ALPL were set to

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Arianna Tucci: Associated with the phenotype

17 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

17 Jul 2018, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: ALPL were set to Hypophosphatasia, adult 146300 AD, AR; Hypophosphatasia, childhood 241510 AR; Hypophosphatasia, infantile 241500 AR; Odontohypophosphatasia 146300 AD, AR

17 Jul 2018, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: ALPL was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

17 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

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

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

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

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

ALPL was created by Sarah Leigh