2. Academic Validation
  3. A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene

A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene

  • Eur J Hum Genet. 2016 Aug;24(8):1206-10. doi: 10.1038/ejhg.2015.261.
Katta Mohan Girisha 1,  Fanny Kortüm 2,  Hitesh Shah 3,  Malik Alawi 4 5 6,  Ashwin Dalal 7,  Gandham SriLakshmi Bhavani 1,  Kerstin Kutsche 2
Affiliations

Affiliations

  • 1 Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
  • 2 Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • 3 Division of Pediatric Orthopedics, Department of Orthopedics, Kasturba Medical College, Manipal University, Manipal, India.
  • 4 University Medical Center Hamburg-Eppendorf, Bioinformatics Service Facility, Hamburg, Germany.
  • 5 Center for Bioinformatics, University of Hamburg, Hamburg, Germany.
  • 6 Heinrich-Pette-Institute, Leibniz-Institute for Experimental Virology, Virus Genomics, Hamburg, Germany.
  • 7 Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
PMID: 26669664 DOI: 10.1038/ejhg.2015.261
Abstract

We report two brothers from a consanguineous couple with spondyloepimetaphyseal dysplasia (SEMD), multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones, probably representing a yet uncharacterized SEMD with laxity and dislocations. This condition has clinical overlap with autosomal dominantly inherited SEMD with joint laxity, leptodactylic type caused by recurrent missense variants in the Kinesin family member 22 gene (KIF22). Single-nucleotide polymorphism array analysis and whole-exome sequencing in the two affected siblings revealed a shared homozygous nonsense variant [c.906T>A/p.(Tyr302*)] in EXOC6B as the most likely cause. EXOC6B encodes a component of the exocyst complex required for tethering secretory vesicles to the plasma membrane. As transport of vesicles from the golgi apparatus to the plasma membrane occurs through Kinesin motor proteins along microtubule tracks, the function of EXOC6B is linked to KIF22 suggesting a common pathogenic mechanism in skeletal dysplasias with joint laxity and dislocations.

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