Myopathic changes associated with psychomotor delay and seizures caused by a novel homozygous mutation in TBCK

Background Biallelic mutations in TBC1‐domain containing kinase (TBCK) lead to hypotonia, global developmental delay with severe cognitive and motor deficits, and variable presentation of dysmorphic facial features and brain malformations. It remains unclear whether hypotonia in these individuals is...

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Bibliographic Details
Published in:Muscle & nerve 2020-08, Vol.62 (2), p.266-271
Main Authors: Saredi, Simona, Cauley, Edmund S., Ruggieri, Alessandra, Spivey, Tyler M., Ardissone, Anna, Mora, Marina, Moroni, Isabella, Manzini, M. Chiara
Format: Article
Language:English
Subjects:
Biopsy
Cognitive ability
Convulsions & seizures
Delay
encephalopathy
exome sequencing
Genotypes
Hypotonia
Immunohistochemistry
Intracellular signalling
Kinases
mTOR signaling
muscle disease
Muscles
Mutation
Phenotypes
Seizures
TBCK
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Summary:Background Biallelic mutations in TBC1‐domain containing kinase (TBCK) lead to hypotonia, global developmental delay with severe cognitive and motor deficits, and variable presentation of dysmorphic facial features and brain malformations. It remains unclear whether hypotonia in these individuals is purely neurogenic, or also caused by progressive muscle disease. Methods Whole exome sequencing was performed on a family diagnosed with nonspecific myopathic changes by means of histological analysis and immunohistochemistry of muscle biopsy samples. Results A novel homozygous truncation in TBCK was found in two sisters diagnosed with muscle disease and severe psychomotor delay. TBCK was completely absent in these patients. Conclusions Our findings identify a novel early truncating variant in TBCK associated with a severe presentation and add muscle disease to the variability of phenotypes associated with TBCK mutations. Inconsistent genotype/phenotype correlation could be ascribed to the multiple roles of TBCK in intracellular signaling and endolysosomal function in different tissues.
ISSN:0148-639X
1097-4598
DOI:10.1002/mus.26907