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Myopathic changes associated with psychomotor delay and seizures caused by a novel homozygous mutation in TBCK
Author(s) -
Saredi Simona,
Cauley Edmund S.,
Ruggieri Alessandra,
Spivey Tyler M.,
Ardissone Anna,
Mora Marina,
Moroni Isabella,
Manzini M. Chiara
Publication year - 2020
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26907
Subject(s) - hypotonia , muscle hypotonia , muscle biopsy , exome sequencing , psychomotor learning , medicine , phenotype , mutation , psychomotor disorder , pathology , genetics , biology , biopsy , cognition , gene , psychiatry
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.