GLI2 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: GLI family zinc finger 2
  • Regulates other genes by binding to specific DNA regions (transcription factor)
  • Mediates SHH signalling during embryonic development
  • SHH is a signalling protein involved in cell growth and specialisation
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal dominant
Ocular features
Systemic featuresHoloprosencephaly 9:
  • Incomplete seperation of forebrain into right and left halves
  • Wide phenotypic spectrum of brain developmental defects +/- overt forebrain cleavage abnormalities
  • Midline craniofacial anomalies involving the first branchial arch and/or the orbits (micro-/macrocephaly, midface hypoplasia, nasal anomalies, cleft lip and/or palate, orbital hypotelorism, ear anomalies)
  • Pituitary hypoplasia leading to panhypopituitarism
  • Postaxial polydactyly
  • Learning difficulties
Key investigations
  • B-scan USS to measure axial length to document microphthalmia
  • Electrophysiology
  • MRI brain and orbit
  • Systemic assessment with a paediatrician and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (MAC)
  • Whole genome sequencing
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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Additional information

Heterozygous GLI2 mutations can manifest as holoprosencephaly 9 with variable expressivity and incomplete penetrance within and between families. This means that some mutation carriers are unaffected, some may be less affected while a small minority display the full disease phenotype. It is estimated that about one-third of obligate carriers of autosomal dominant holoprosencephaly are asymptomatic with normal cognitive function.[5]

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  1.  Bertolacini CD, Ribeiro-Bicudo LA, Petrin A, Richieri-Costa A, Murray JC. Clinical findings in patients with GLI2 mutations–phenotypic variability. Clin Genet. 2012;81(1):70‐75
  2.  Roessler E, Du YZ, Mullor JL, et al. Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features. Proc Natl Acad Sci. 2003;100(23):13424‐13429
  3.  Varjosalo M, Björklund M, Cheng F, et al. Application of active and kinase-deficient kinome collection for identification of kinases regulating hedgehog signaling. Cell. 2008;133(3):537‐548
  4.  Rahimov F, Ribeiro LA, de Miranda E, Richieri-Costa A, Murray JC. GLI2 mutations in four Brazilian patients: how wide is the phenotypic spectrum?. Am J Med Genet A. 2006;140(23):2571‐2576
  5.  Ming JE, Kaupas ME, Roessler E, et al. Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly [published correction appears in Hum Genet 2002 Oct;111(4-5):464]. Hum Genet. 2002;110(4):297‐301

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Updated on November 30, 2020
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