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

Katta Mohan Girisha, Fanny Kortüm, Hitesh Shah, Malik Alawi, Ashwin Dalal, Gandham Sri Lakshmi Bhavani, Kerstin Kutsche

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1206-1210
Number of pages5
JournalEuropean Journal of Human Genetics
Volume24
Issue number8
DOIs
Publication statusPublished - 01-08-2016

Fingerprint

Kinesin
Joint Dislocations
Joint Instability
Siblings
Tarsal Bones
Cell Membrane
Carpal Bones
Genes
Microtubule Proteins
Exome
Transport Vesicles
Metacarpal Bones
Metatarsal Bones
Secretory Vesicles
Scoliosis
Golgi Apparatus
Single Nucleotide Polymorphism
Parturition

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Girisha, Katta Mohan ; Kortüm, Fanny ; Shah, Hitesh ; Alawi, Malik ; Dalal, Ashwin ; Bhavani, Gandham Sri Lakshmi ; Kutsche, Kerstin. / A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene. In: European Journal of Human Genetics. 2016 ; Vol. 24, No. 8. pp. 1206-1210.
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A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene. / Girisha, Katta Mohan; Kortüm, Fanny; Shah, Hitesh; Alawi, Malik; Dalal, Ashwin; Bhavani, Gandham Sri Lakshmi; Kutsche, Kerstin.

In: European Journal of Human Genetics, Vol. 24, No. 8, 01.08.2016, p. 1206-1210.

Research output: Contribution to journalArticle

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