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Neurol Genet. 2016 May 24;2(3):e76. doi: 10.1212/NXG.0000000000000076. eCollection 2016 Jun.

Mutation of TBCK causes a rare recessive developmental disorder.

Author information

1
Department of Molecular Neuroscience (R.J.G., J.B.), Institute of Neurology; MRC Laboratory for Molecular Cell Biology (R.B., S.E.M.), University College London; Manchester Centre for Genomic Medicine (D.D.), University of Manchester and Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust; Royal Preston Hospital (C.d.G.), Genetics and Genomics Medicine Programme (S.E.M.), UCL Institute of Child Health and Department of Genetics, Evolution and Environment, University College London, UK.

Abstract

OBJECTIVE:

To characterize the underlying genetic defect in a family with 3 siblings affected by a severe, yet viable, congenital disorder.

METHODS:

Extensive genetic and metabolic investigations were performed, and the affected children were imaged at different ages. Whole-genome genotyping and whole-exome sequencing were undertaken. A single large region (>8 Mb) of homozygosity in chromosome 4 (chr4:100,268,553-108,609,628) was identified that was shared only in affected siblings. Inspection of genetic variability within this region led to the identification of a novel mutation. Sanger sequencing confirmed segregation of the mutation with disease.

RESULTS:

All affected siblings share homozygosity for a novel 4-bp deletion in the gene TBCK (NM_033115:c.614_617del:p.205_206del).

CONCLUSIONS:

This finding provides the genetic cause of a severe inherited disease in a family and extends the number of mutations and phenotypes associated with this recently identified disease gene.

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