ABSTRACT
Variants in the KIF1A gene can cause autosomal recessive spastic paraplegia 30, autosomal recessive hereditary sensory neuropathy, or autosomal (de novo) dominant mental retardation type 9. More recently, variants in KIF1A have also been described in a few cases with autosomal dominant spastic paraplegia. Here, we describe 20 KIF1A variants in 24 patients from a clinical exome sequencing cohort of 347 individuals with a mostly 'pure' spastic paraplegia. In these patients, spastic paraplegia was slowly progressive and mostly pure, but with a highly variable disease onset (0-57 years). Segregation analyses showed a de novo occurrence in seven cases, and a dominant inheritance pattern in 11 families. The motor domain of KIF1A is a hotspot for disease causing variants in autosomal dominant spastic paraplegia, similar to mental retardation type 9 and recessive spastic paraplegia type 30. However, unlike these allelic disorders, dominant spastic paraplegia was also caused by loss-of-function variants outside this domain in six families. Finally, three missense variants were outside the motor domain and need further characterization. In conclusion, KIF1A variants are a frequent cause of autosomal dominant spastic paraplegia in our cohort (6-7%). The identification of KIF1A loss-of-function variants suggests haploinsufficiency as a possible mechanism in autosomal dominant spastic paraplegia.
Subject(s)
Kinesins/genetics , Spastic Paraplegia, Hereditary/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Genes, Dominant , Humans , Infant , Kinesins/chemistry , Male , Middle Aged , Mutation, Missense , Pedigree , Protein Domains , Spastic Paraplegia, Hereditary/pathologyABSTRACT
We present a case of postdural puncture headache in a patient with extensive epidural fluid accumulation. An initial epidural blood patch was aborted because of concern about increased risk of complications. After magnetic resonance imaging, we proceeded with epidural blood patch with a good therapeutic result. We discuss the imaging results and safety concerns we considered when assessing the benefits and risks of epidural blood patch in this patient.
Subject(s)
Blood Patch, Epidural/methods , Post-Dural Puncture Headache/therapy , Adult , Blood Patch, Epidural/adverse effects , Epidural Space/pathology , Female , Humans , Injections, Epidural , Magnetic Resonance Imaging , Treatment OutcomeABSTRACT
We describe a patient who presented with loss of vision that turned out to be caused by cobalamin deficiency. Both her vision and her visual field improved upon supplementation of cobalamin. It is, therefore, important to consider cobalamin deficiency as a treatable cause of loss of vision.
