PITX3 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: paired like homeodomain 3
  • Regulates other genes by binding to specific DNA regions (transcription factor)
  • A crucial protein involved in lens formation during ocular development
  • Maintains cell division in the developing lens, partially through regulation of FOXE3 and PROX1
Clinical phenotype
(OMIM phenotype no.)
  • Cataract 11, multiple subtypes (#610623)
  • Cataract 11, syndromic, autosomal recessive (#610623)
  • Anterior segment dysgenesis 1, multiple subtypes (#107250)
  • Autosomal dominant
  • Autosomal recessive
Ocular features
Systemic features
  • Two children with homozygous c.650delG mutations from a consaingeneous marriage displayed neurologic features in addition to ocular phenotypes
  • Intellectual disability
  • Developmental delays
  • Choreiform movements
  • Hypertonia
  • Decreased deep tendon reflexes in the lower extremities
Key investigations
  • B-scan USS to measure axial length to document microphthalmia and detect any posterior abnormalities in congenital cataract cases
  • Electrophysiology
  • TORCH screen for children with congenital cataract
  • Ultrasound biomicroscopy and/or anterior segment OCT to detect anterior segment abnormalities if corneal opacity is present
  • Glaucoma assessment (tonometry, pachymetry, perimetry, gonioscopy if indicated and optic disc imaging)
  • MRI brain and orbit may be indicated if MAC and/or neurologic features are present
  • Systemic assessment with a paediatrician and other relevant specialists if indicated
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (MAC/congenital cataract/ASD)
  • Whole genome sequencing
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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  1.  Berry V, Yang Z, Addison PK, et al. Recurrent 17 bp duplication in PITX3 is primarily associated with posterior polar cataract (CPP4). J Med Genet. 2004;41(8):e109
  2.  Bidinost C, Matsumoto M, Chung D, et al. Heterozygous and homozygous mutations in PITX3 in a large Lebanese family with posterior polar cataracts and neurodevelopmental abnormalities. Invest Ophthalmol Vis Sci. 2006;47(4):1274-1280
  3.  Cheong SS, Hentschel L, Davidson AE, et al. Mutations in CPAMD8 Cause a Unique Form of Autosomal-Recessive Anterior Segment Dysgenesis. Am J Hum Genet. 2016;99(6):1338-1352
  4.  Medina-Martinez O, Shah R, Jamrich M. Pitx3 controls multiple aspects of lens development. Dev Dyn. 2009;238(9):2193-2201
  5.  Anand D, Agrawal SA, Slavotinek A, Lachke SA. Mutation update of transcription factor genes FOXE3, HSF4, MAF, and PITX3 causing cataracts and other developmental ocular defects. Hum Mutat. 2018;39(4):471-494
  6.  Aldahmesh MA, Khan AO, Mohamed J, Alkuraya FS. Novel recessive BFSP2 and PITX3 mutations: insights into mutational mechanisms from consanguineous populations. Genet Med. 2011;13(11):978-981
  7.  Semina EV, Ferrell RE, Mintz-Hittner HA, et al. A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. Nat Genet. 1998;19(2):167-170
  8.  Verdin H, Sorokina EA, Meire F, et al. Novel and recurrent PITX3 mutations in Belgian families with autosomal dominant congenital cataract and anterior segment dysgenesis have similar phenotypic and functional characteristics. Orphanet J Rare Dis. 2014;9:26

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Updated on November 30, 2020
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