Whole-exome sequencing reveals a novel frameshift and a recurrent nonsense SPG11 variant causing rare familial amyotrophic lateral sclerosis type 5 in two consanguineous Pakistani families.
Riaz Ahmad, Muhammad Naeem, Henry Houlden
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From the abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both upper and lower motor neurons, disturbing communication between the brain and muscles. So far, few reports have been published for the SPG11-associated ALS, and this is the first documented case from Pakistan.  METHODS: We report a rare subtype of ALS with an autosomal recessive mode of…
Reported results
Two homozygous variants within the SPG11 gene were identified as pathogenic according to the ACMG and ClinGen Sequence Variant Interpretation (SVI) Working Group recommendations: a novel truncation (NM_025137.4:c.6738dup, p.Glu2247Ter) variant as validated by Sanger sequencing and a recurrent nonsense (NM_025137.4: c.782C>A, p.Ser261Ter) variant (rs765477482) previously reported in a family affected with…
Authors' conclusions
Five patients with juvenile-onset ALS born to consanguineous parents were found to have homozygous SPG11 gene variants. Our findings describe the overlapping phenotypes ofSPG11-related autosomal recessive juvenile ALS and ARHSP, suggesting that these disorders show a clear overlapping phenotype with common genetic defects. In clinical practice, it is challenging to distinguish between these two disorders.