Co-occurrence of leukoencephalopathy with ataxia and SPG56 in one family

Forskningsoutput: TidskriftsbidragPublicerat konferensabstractPeer review


Objective: We describe an Iraqi family with two recessive movement disorders, leukoencephalopathy with ataxia caused by CLCN2 mutations (LKPAT) and autosomal recessive spastic paraplegia 56 (SPG56) caused by mutations in CYP2U1. Methods: Members of an Iraqi family underwent structured interviews and neurological examination. Neuroimaging and whole exome sequencing were performed, and medical records reviewed. Results: Two (II:2, II:4; Figure) out of four siblings examined had spastic paraplegia, cognitive impairment, bladder and bowel dysfunction and gait ataxia. The parents were consanguineous and clinically unaffected. Brain MRI showed T2-weighted hyperintensities and T1-weighted hypointensities in the internal capsules, cerebral peduncles, pyramidal tracts and middle cerebellar peduncles. Both affected patients were homozygous for CYP2U1 c.947A>T p.(Asp316Val), a known cause for SPG56. However, both were also homozygous for a novel CLCN2 c.607G>T, p.(Gly203Cys) variant, classified as a variant of unknown significance. Genetic testing of 4 additional family members revealed homozygosity for the CLCN2 variant also in II:1 whom we initially considered unaffected. Both II:1 and II:4 were infertile, and review of the literature revealed one reported case with LKPAT and azoospermia. II:1 had been examined with testicular biopsy, showing incomplete maturation arrest in spermatogenesis. On clinical examination we found mild memory impairment and hand tremor. MRI showed similar changes to his siblings. Conclusions: We consider the homozygous CLCN2 mutation c.607G>T, p.(Gly203Cys) pathogenic because of the typical neuroradiological and clinical findings in this family. New Generation Sequencing can detect co-occurrence of genetic disorders. Considerable workup can be required to determine the pathogenicity of novel variants.
ArtikelnummerA 401
Sidor (från-till)e112-e113
TidskriftParkinsonism & Related Disorders
StatusPublished - 2020
Externt publiceradJa

Ämnesklassifikation (UKÄ)

  • Neurologi


Utforska forskningsämnen för ”Co-occurrence of leukoencephalopathy with ataxia and SPG56 in one family”. Tillsammans bildar de ett unikt fingeravtryck.

Citera det här