Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kinesins are a large superfamily of molecular motors. They move along microtubule filaments and are powered by the hydrolysis of ATP. This transport system is essential for neuronal function and survival. KIF1A belongs to the kinesin 3 family and involves in the anterograde transport of synaptic vesicle precursors along axons. Several studies confirmed that KIF1A mutations cause spastic paraplegia and sensory neuropathy in an autosomal-recessive fashion. A missense mutation in the KIF1A gene (p.Thr99Met) has been reported in a patient with intellectual disability (ID), axial hypotonia and peripheral spasticity. Mild atrophy of the cerebellar vermis was found on magnetic resonance imaging. The mutation was heterozygous and de novo. We identified the second patient with the p.T99M mutation in the KIF1A gene by whole-exome sequencing. He showed severe ID, spasticity, optic atrophy, neurogenic bladder, growth failure and progressive cerebellar atrophy. The p.T99M mutation may be a common recurrent mutation. We suppose that this specific mutation of KIF1A shows a novel neurodegenerative syndrome.
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PMID:KIF1A mutation in a patient with progressive neurodegeneration. 2525 58

We report a child with hypotonia, optic atrophy, progressive encephalopathy and intractable infantile spasms who was diagnosed with PEHO syndrome. Extensive investigation was performed to diagnose an underlying etiology. Electron transport chain activities in muscle biopsies showed an isolated complex IV deficiency. Genetic examination focused on complex IV genes such as mtDNA and relevant nuclear DNA analysis was unremarkable. Whole exome sequencing with trio revealed a heterozygous de novo mutation at c.757G>A (p.E253K) in the KIF1A gene. The protein encoded by this gene functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. The relation between this genetic mutation and decreased activity of the mitochondrial respiratory chain complex is discussed in details. Our study further confirmed that the molecular basis of PEHO syndrome at least in a subset of patients is a dominant KIF1A variant affecting the motor domain of the protein. This is the first description of the decreased activity of mitochondrial respiratory chain complex in association with either PEHO syndrome or KIF1A mutation. This study emphasizes that the results of the mitochondrial enzymes should be interpreted with caution and clinicians should be actively looking for other underlying diagnoses with further comprehensive studies.
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PMID:PEHO syndrome: KIF1A mutation and decreased activity of mitochondrial respiratory chain complex. 3038 66