Hereditary spastic paraplegia - childhood onset

Gene: GJA1

Amber List (moderate evidence)

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

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Regarding inclusion of this gene on the childhood-onset panel, Helen Brittain (Genomics England Clinical Team) suggests - "As you say, there are sufficient cases albeit seemingly edge cases. I would be inclined to include it on the paediatric panel, as they are outlining the spasticity as a feature of ODDD, rather than a separate clinical entity. ODDD would be a paediatric-age diagnosis to make and the fact that it is clinically recognisable could aid in interpretation of variants of uncertain significance"
Created: 25 Oct 2021, 10:11 a.m. | Last Modified: 25 Oct 2021, 10:11 a.m.
Panel Version: 2.85
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

25 Oct 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: GJA1 were set to 18660473; 22214631; 29927410; 31023660; 33190326; 33612672

25 Oct 2021, Gel status: 2

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

Arina Puzriakova (Genomics England Curator)

gene: GJA1 was added gene: GJA1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert list,Expert Review Amber Q3_21_rating tags were added to gene: GJA1. Mode of inheritance for gene: GJA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GJA1 were set to 18660473; 22214631; 29927410; 31023660; 33190326; 33612672 Phenotypes for gene: GJA1 were set to Oculodentodigital dysplasia, OMIM:164200; Spastic paraplegia