Hereditary spastic paraplegia - childhood onset

Gene: ARL6IP1

Amber List (moderate evidence)

ARL6IP1 (ADP ribosylation factor like GTPase 6 interacting protein 1)
EnsemblGeneIds (GRCh38): ENSG00000170540
EnsemblGeneIds (GRCh37): ENSG00000170540
OMIM: 607669, Gene2Phenotype
ARL6IP1 is in 6 panels

4 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Leaving rating as amber but with recommendation for promotion to green at the next review. 4 cases reported with 3 different variants.
Created: 30 Jun 2021, 2:25 p.m. | Last Modified: 30 Jun 2021, 2:25 p.m.
Panel Version: 2.42
Provisionally associated with ?Spastic paraplegia 61, autosomal recessive #615685 in OMIM. (AR)

PMID: 24482476 - Novarino et al 2014 - analyzed 55 families displaying autosomal recessive-Hereditary spastic paraplegia by whole-exome sequencing. Found a homozygous 4bp deletion in ARL6IP1 causing a frameshift in 1 consanguineous family with 2 siblings (both with age of onset at 14 months).

PMID: 31272422 - Wakil et al 2019 - report a consanguineous Saudi family with 2 siblings with a severe presentation of spastic paraplegia with many additional phenotypic components, which resulted in death of both affected siblings in early childhood. A homozygous nonsense variant ARL6IP1 (NM_015161.1: c.112C > T: p.Arg38*) was identified by homozygosity mapping and WES. The authors speculate that other variants may contribute to the severe clinical presentation in this family.

PMID: 30980493 - Chukhrova et al 2019 - report a consanguineous Russian family with 2 brothers with childhood onset spastic paraplegia. A homozygous variant c.[92T>C], p.[Leu31Pro] in ARL6IP1 was identified by WES. Sanger sequencing confirmed the variant was heterozygous in each parent.

PMID: 28471035 - Nizon et al 2018 - describe a patient with congenital insensitivity to pain, sensory neuropathy, acromutilation, and spastic paraplegia. Parents were second-cousins of Caucasian descent. A homozygous frameshift variant c.[577_580del], p.(Lys193Phefs*37) in ARL6IP1 was identified by WES (same variant as reported by Novarino). The unaffected mother and 1 sibling were heterozygous. Father's DNA was not available.
Created: 30 Jun 2021, 2:24 p.m. | Last Modified: 30 Jun 2021, 2:24 p.m.
Panel Version: 2.41

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 61, autosomal recessive, OMIM:615685

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

At least 4 families reported now.
Created: 16 Jun 2020, 10:54 a.m. | Last Modified: 16 Jun 2020, 10:54 a.m.
Panel Version: 2.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 61, autosomal recessive, MIM#615685

Publications

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

Louise Daugherty (Genomics England Curator)

I don't know

Red gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Created: 21 May 2019, 4:50 p.m.

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

Green List (high evidence)

Appears to be childhood onset only. Two kindred reported but Novarino et al 2014 kindred with 4 affected individuals from 2 branches of family. No additional patients identified using Sheffield panel.
Created: 10 May 2019, 11:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
24482476; 28471035

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • NHS GMS
  • Yorkshire and North East GLH
  • Expert list
Phenotypes
  • Spastic paraplegia 61, autosomal recessive, OMIM:615685
  • hereditary spastic paraplegia 61, MONDO:0014304
Tags
Q2_21_rating
OMIM
607669
Clinvar variants
Variants in ARL6IP1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

30 Jun 2021, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: ARL6IP1 were changed from Spastic paraplegia to Spastic paraplegia 61, autosomal recessive, OMIM:615685; hereditary spastic paraplegia 61, MONDO:0014304

30 Jun 2021, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: ARL6IP1 were set to Novarino et al. (2014); 24482476; 28471035

30 Jun 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: arl6ip1 has been classified as Amber List (Moderate Evidence).

30 Jun 2021, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: ARL6IP1.

21 May 2019, Gel status: 2

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Amber was added to ARL6IP1. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)

13 May 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: ARL6IP1 were changed from to Spastic paraplegia

13 May 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: ARL6IP1 were set to Novarino et al. (2014)

13 May 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to ARL6IP1.

13 May 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to ARL6IP1.

28 Jan 2019, Gel status: 1

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Rebecca Foulger: Comment on list classification

19 Dec 2018, Gel status: 1

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

Sarah Leigh (Genomics England Curator)

gene: ARL6IP1 was added gene: ARL6IP1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert list,Expert Review Red Mode of inheritance for gene: ARL6IP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARL6IP1 were set to Novarino et al. (2014)