Hereditary spastic paraplegia - adult onset

Gene: GJA1

Green List (high evidence)

GJA1 (gap junction protein alpha 1)
EnsemblGeneIds (GRCh38): ENSG00000152661
EnsemblGeneIds (GRCh37): ENSG00000152661
OMIM: 121014, Gene2Phenotype
GJA1 is in 25 panels

3 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 14 Mar 2022, 1:19 p.m. | Last Modified: 14 Mar 2022, 1:19 p.m.
Panel Version: 1.95

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Progressive neurological symptoms are occasionally seen in ODDD due to degeneration of the white matter tracts and can include spastic paraplegia. Gait disturbances due to spasticity can be a presenting feature for which patients initially seek medical attention. Typically signs of spasticity arise in adulthood (PMID: 18660473; 22214631; 29927410; 31023660; 33190326; 33612672); however, several adolescent onset cases (PMID: 18660473; 31023660) have also been described and I could only find a single childhood-onset case with spasticity arising at age 8 (PMID: 29927410).

Overall there is enough evidence to rate as Green on the adult-onset HSP panel (>10 unrelated families reported in literature). I will seek further clinical opinion with regard to inclusion on the childhood-onset panel given the implications of carrier status being found incidentally for this primarily adult-onset condition.
Created: 1 Sep 2021, 10:50 a.m. | Last Modified: 1 Sep 2021, 11:10 a.m.
Panel Version: 1.72

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Oculodentodigital dysplasia, OMIM:164200

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

8 individuals from 5 families with oculodentodigital dysplasia presenting in adulthood with onset of spastic paraplegia and white matter changes on imaging.
Sources: Expert list
Created: 20 Sep 2020, 8:35 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hereditary spastic paraplegia; Oculodentodigital dysplasia, MIM#164200

Publications

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

History Filter Activity

14 Mar 2022, Gel status: 3

Removed Tag

Ivone Leong (Genomics England Curator)

Tag Q3_21_rating was removed from gene: GJA1.

14 Mar 2022, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Green was added to GJA1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

1 Sep 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: gja1 has been classified as Amber List (Moderate Evidence).

1 Sep 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_21_rating tag was added to gene: GJA1.

1 Sep 2021, Gel status: 0

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: GJA1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

1 Sep 2021, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: GJA1 were changed from Hereditary spastic paraplegia; Oculodentodigital dysplasia, MIM#164200 to Oculodentodigital dysplasia, OMIM:164200; Spastic paraplegia

1 Sep 2021, Gel status: 0

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: GJA1 were set to 31023660

20 Sep 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: GJA1 was added gene: GJA1 was added to Hereditary spastic paraplegia - adult onset. Sources: Expert list Mode of inheritance for gene: GJA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GJA1 were set to 31023660 Phenotypes for gene: GJA1 were set to Hereditary spastic paraplegia; Oculodentodigital dysplasia, MIM#164200 Review for gene: GJA1 was set to GREEN gene: GJA1 was marked as current diagnostic