Hereditary spastic paraplegia

Gene: ABCD1

Green List (high evidence)

ABCD1 (ATP binding cassette subfamily D member 1)
EnsemblGeneIds (GRCh38): ENSG00000101986
EnsemblGeneIds (GRCh37): ENSG00000101986
OMIM: 300371, Gene2Phenotype
ABCD1 is in 16 panels

3 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Red to Green. ABCD1 was added to panel and rated Green by Chris Buxton (Bristol NHS). Sufficient unrelated cases (>3) of patients with HSP phenotype and ABCD1 variant to support causation of spastic paraplegia (see comments on individual papers for details).
Created: 7 Jan 2019, 1:17 p.m.
O'Neill (2001, 11739809) identify a large kindred with AMN phenotype resembling X-linked dominant HSP. All obligate female carriers were clinically affected. A deletion of the ABCD1 gene ATG translation initiaion codon was detected leading to an N-terminally truncated protein.
Created: 7 Jan 2019, 1:15 p.m.
Koutsis (2015, 26049658) report a Greek family with 5 males and 2 females developing progressive spastic paraplegia. NGS of the proband revealed a novel frameshift mutation in ABCD1 (c.1174_1178del, p.Leu392Serfs*7), which segregated in all family members.
Created: 7 Jan 2019, 1:15 p.m.
Zhan 2013 (PMID:23664929) investigated a Chinese family with recessive HSP. A missense variant (c.1661G>A, p.R554H) was identified in ABCD1, which co-segregated with the disease.
Created: 7 Jan 2019, 1:15 p.m.
Balicza (2016, 27084228) carried out genetic testing for 58 probands with clinical features of HSP. Results included one hemizygous variant in ABCD1 (c.1553G>C, p.Arg518Pro) in a male patient with sporadic spastic paraparesis. His disease started at age 28. The authors report that there are other similar cases where ABCD1 variants mimic HSP.
Created: 7 Jan 2019, 1:15 p.m.
PMID:11810273 (Guimaraes 2001) studied two X-ALD patients and identified splice-site variants in ABCD1. Both Patients (A and B) were males with an original diagnosis of Addison disease, with a later diagnosis of spastic paraparesis following muscular weakness and difficulty walking.
Created: 7 Jan 2019, 1:14 p.m.

Sarah Leigh (Genomics England Curator)

Comment on list classification: This gene is awaiting curator evaluation and rating.
Created: 19 Dec 2018, 2:10 p.m.

Chris Buxton (North Bristol NHS Trust)

Green List (high evidence)

Guimarães (2001, 11810273), X-linked adrenoleukodystrophy.
Spastic paraparesis with neurophysiologic abnormalities with an altered spinal cord MRI and a normal cerebral MRI. 2 different splice variants described

Balicza (2016, 27084228), hereditary spastic paraplegia phenotype
Spastic paraparesis; c.1553G>C p.R518P (no details)

O'Neill (2001, 11739809), X-linked dominant hereditary spastic paraparesis
Obligate female carriers affected, deletion 26 bp nt. 369-394, 5'UTR-cd.3

Koutsis (2015, 26049658) progressive spastic paraplegia with raised VLCFA, ABCD1 (c.1174_1178del, p.Leu392Serfs*7)

Gene is on Sheffield's HSP panel
Sources: Literature
Created: 27 Nov 2018, 12:56 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation

Publications

History Filter Activity

7 Jan 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: abcd1 has been classified as Green List (High Evidence).

7 Jan 2019, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: ABCD1 were changed from Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation; spastic paraparesis to Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation; spastic paraparesis; Adrenoleukodystrophy, 300100

7 Jan 2019, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: ABCD1 were changed from Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation to Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation; spastic paraparesis

7 Jan 2019, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: ABCD1 were set to

19 Dec 2018, Gel status: 1

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: abcd1 has been classified as Red List (Low Evidence).

27 Nov 2018, Gel status: 0

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

Chris Buxton (North Bristol NHS Trust)

gene: ABCD1 was added gene: ABCD1 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: ABCD1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: ABCD1 were set to Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation Penetrance for gene: ABCD1 were set to unknown Review for gene: ABCD1 was set to GREEN