TBC1D20 gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: TBC1 domain family member 20
  • Regulates the activity of GTPases such as RAB18 and RAB1
  • RAB18 is involved in intracellular vesicle trafficking, structural organization and cell autophagy
  • RAB1 maintains the structure of Golgi apparatus
Clinical phenotype
(OMIM phenotype no.)
Inheritance
  • Autosomal recessive
Ocular features
Systemic features
  • Structural abnormalities of the brain (postnatal microcephaly, polymicrogyria, corpus callosum hypogenesis, cerebellar vermis hypoplasia)
  • Seizures
  • Facial anomalies (wide nasal bridge, relatively narrow mouth and prominent subnasal region)
  • Limb hypotonia in infancy progressing to spastic quadriplegia later in life
  • Hypothalamic hypogonadism (micropenis and cryptorchidismin in boys; hypoplastic labia minora and clitorial hypoplasia in girls)
  • Severe developmental delays
Key investigations
  • B-scan USS to measure axial length to document microphthalmia and detect any posterior segment abnormalities
  • Electrophysiology
  • TORCH screen for children with congenital cataract
  • MRI brain and orbit
  • Systemic assessment with a paediatrician and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (MAC, cataract and/or optic atrophy)
  • Whole genome sequencing
ManagementOcularSystemic
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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References

  1.  Liegel RP, Handley MT, Ronchetti A, et al. Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. Am J Hum Genet. 2013;93(6):1001-1014
  2.  Feldmann A, Bekbulat F, Huesmann H, et al. The RAB GTPase RAB18 modulates macroautophagy and proteostasis. Biochem Biophys Res Commun. 2017;486(3):738-743
  3.  Gerondopoulos A, Bastos RN, Yoshimura S, et al. Rab18 and a Rab18 GEF complex are required for normal ER structure. J Cell Biol. 2014;205(5):707-720
  4.  Haas AK, Yoshimura S, Stephens DJ, Preisinger C, Fuchs E, Barr FA. Analysis of GTPase-activating proteins: Rab1 and Rab43 are key Rabs required to maintain a functional Golgi complex in human cells. J Cell Sci. 2007;120(Pt 17):2997-3010

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Updated on November 30, 2020
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