Hereditary spastic paraplegia - childhood onset

Gene: IBA57

Amber List (moderate evidence)

IBA57 (IBA57 homolog, iron-sulfur cluster assembly)
EnsemblGeneIds (GRCh38): ENSG00000181873
EnsemblGeneIds (GRCh37): ENSG00000181873
OMIM: 615316, Gene2Phenotype
IBA57 is in 14 panels

3 reviews

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

I don't know

Three families reported with childhood onset. No additional patients identified using Sheffield panel.
Created: 9 May 2019, 5:38 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Louise Daugherty (Genomics England Curator)

I don't know

Amber 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.
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 4:54 p.m.
Amber rating on Hereditary spastic paraplegia panel 1.198

Comment on list classification: Kept rating as Amber following clinical review by Helen Brittain, who notes that it is possible that the varied phenotypes are part of the spectrum of presentations within IBA57 regarding its mitochondrial function (the more commonly reported recessive phenotype of mitochondrial dysfunction encompasses spasticity in several patients). IBA57 is green on the 'Mitochondrial disorders' panel which is the better route for detecting this broader phenotype. Ideally, further cases with an understanding of the spectrum of pathogenic variants and detailed phenotypic information will help in being confident about inclusion on this HSP panel.
Rebecca Foulger (Genomics England curator), 2 Mar 2019

Comment on list classification: Updated rating from Grey to Amber: Gene added and rated Red by Chris Buxton (Bristol NHS) based on 1 family in PMID:25609768. 2 additional families in PMID:30258207 (2018) but phenotype is variable and 2 Jewish brothers with same compound het variants have different symptoms. Therefore rated Amber awaiting clinical feedback.
Rebecca Foulger (Genomics England curator), 18 Dec 2018

PMID:30258207 (Hamanaka et al, 2018) performed whole-exome sequencing in 2 unrelated families (Sepharadi Jewish and Japanese) with leukodystrophy. The 29-year-old Sepharadi Jewish male had clinically asymptomatic leukodystrophy. His 19-year-old younger brother, with the same compound heterozygous IBA57 variants, had a similar clinical course until 7 years of age when he developed a rapidly progressive spastic paraparesis following a febrile illness. A 7-year-old Japanese girl had developmental regression, spastic quadriplegia, and abnormal periventricular white matter. Therefore HSP symptoms amongst the individuals but phenotypes are very varied.
Rebecca Foulger (Genomics England curator), 18 Dec 2018

In affected members of a large consanguineous Arab family with AR spastic paraplegia, Lossos et al. (2015, PMID:25609768) identified a homozygous splice site variant in IBA57.
Rebecca Foulger (Genomics England curator), 18 Dec 2018

Lossos (2015, 25609768). Homozygous donor splice-site mutation in the IBA57. mRNA studies done, some protein studies support pathogenicity. 1 family, limited evidence. Sources: Literature Provided in Sheffield Lab diagnostic HSP panel
Chris Buxton (North Bristol NHS Trust), 27 Nov 2018. Red rating submitted.
Created: 2 May 2019, 4:04 p.m.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

Victoria-spasticity, optic atrophy, and peripheral neuropathy in the first decade, in sheffields HSP panel
Created: 28 Apr 2019, 4:16 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Spastic paraplegia 74, autosomal recessive, 616451

History Filter Activity

13 May 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to IBA57.

2 May 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: iba57 has been classified as Amber List (Moderate Evidence).

28 Apr 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: iba57 has been classified as Green List (High Evidence).

28 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to IBA57.

28 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to IBA57.

3 Apr 2019, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes ?Spastic paraplegia 74, autosomal recessive, 616451 for gene: IBA57

28 Jan 2019, Gel status: 2

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Arianna Tucci: Onset of SPG13 is variable: 3

19 Dec 2018, Gel status: 2

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

Sarah Leigh (Genomics England Curator)

gene: IBA57 was added gene: IBA57 was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Amber,Literature Mode of inheritance for gene: IBA57 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IBA57 were set to 30258207; 25609768 Phenotypes for gene: IBA57 were set to ?Spastic paraplegia 74, autosomal recessive, 616451