Childhood onset hereditary spastic paraplegia
Gene: ARL6IP1The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.Created: 14 Mar 2022, 1:30 p.m. | Last Modified: 14 Mar 2022, 1:30 p.m.
Panel Version: 2.130
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
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
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.
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
Tag Q2_21_rating was removed from gene: ARL6IP1.
Source Expert Review Green was added to ARL6IP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: ARL6IP1 were changed from Spastic paraplegia to Spastic paraplegia 61, autosomal recessive, OMIM:615685; hereditary spastic paraplegia 61, MONDO:0014304
Publications for gene: ARL6IP1 were set to Novarino et al. (2014); 24482476; 28471035
Gene: arl6ip1 has been classified as Amber List (Moderate Evidence).
Tag Q2_21_rating tag was added to gene: ARL6IP1.
Source Expert Review Amber was added to ARL6IP1. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Phenotypes for gene: ARL6IP1 were changed from to Spastic paraplegia
Publications for gene: ARL6IP1 were set to Novarino et al. (2014)
Source NHS GMS was added to ARL6IP1.
Source Yorkshire and North East GLH was added to ARL6IP1.
Rebecca Foulger: Comment on list classification
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)