Hereditary spastic paraplegia

Gene: IBA57

I don't know

Gene to be reviewed again after the GMS Neurology specialist test group have reviewed and agreed rating of gene on the Hereditary spastic paraplegia - childhood onset panel on May 2019

Created: 3 May 2019, 8:35 a.m.

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.

Created: 2 Mar 2019, 3:34 p.m.

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.

Created: 18 Dec 2018, 10:08 a.m.

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.

Created: 18 Dec 2018, 9:43 a.m.

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.

Created: 18 Dec 2018, 9:43 a.m.

Red List (low evidence)

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

Created: 27 Nov 2018, 1:20 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
spastic paraplegia

Publications

• 25609768