PTCH1 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: patched 1
  • A receptor for the sonic hedgehog (SHH) protein
  • SHH is a signalling protein involved in cell growth and specialisation, and also in normal shaping (patterning) of the body
Clinical phenotype
(OMIM phenotype no.)
  • Basal cell nevus syndrome (#109400)
  • Also known as Gorlin syndrome
  • Basal cell carcinoma, somatic (#605462)
  • Holoprosencephaly 7 (#610828)
  • Autosomal dominant
Ocular featuresBasal cell nevus syndrome/Gorlin syndrome:Holoprosencephaly 7:
  • Microphthalmia, anophthalmia, coloboma (MAC) spectrum
  • Orbital hypotelorism
  • Cyclopia
Systemic featuresHoloprosencephaly 7:
  • 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
  • Learning difficulties
Basal cell nevus syndrome/Gorlin syndrome:
  • Basal cell carcinoma during adolescence or early adulthood
  • Keatocysts ondotogenic tumours (benign jaw tumours)
  • Higher risk of developing other tumours (childhood medulloblastoma, foetal rhabdomyoma, ovarian fibroma, cardiac fibroma)
  • Palmar and plantar pits
  • Craniofacial (macrocephaly, calcified dural folds, cleft lip/palate)
  • Skeletal (bifid/hypoplastic/synostotic ribs, kyphoscoliosis, abnormal cervical vertebrae, cortical bone defects)
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

Deletion or loss-of-function mutations (null variants) of PTCH1 result in Gorlin syndrome while gain-of-function mutations (a mutation causing the resultant gene product to have a new molecular function) are hypothesised to manifest as holoprosencephaly 7.[6] Among those with holoprosencephaly, there is variable expressivity and incomplete penetrance within and between families. It is estimated that about one-third of obligate carriers of autosomal dominant forms of holoprosencephaly are asymptomatic with normal cognitive function.[7]

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  1.  Chassaing N, Davis EE, McKnight KL, et al. Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network. Genome Res. 2016;26(4):474‐485
  2.  Koch CA, Chrousos GP, Chandra R, et al. Two-hit model for tumorigenesis of nevoid basal cell carcinoma (Gorlin) syndrome-associated hepatic mesenchymal tumor. Am J Med Genet. 2002;109(1):74‐76
  3.  Ma G, Yu J, Xiao Y, et al. Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels. Cell Res. 2011;21(9):1343‐1357
  4.  Marigo V, Davey RA, Zuo Y, Cunningham JM, Tabin CJ. Biochemical evidence that patched is the Hedgehog receptor. Nature. 1996;384(6605):176‐179
  5.  Evans DG, Farndon PA, Burnell LD, Gattamaneni HR, Birch JM. The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. Br J Cancer. 1991;64(5):959‐961
  6.  Derwińska K, Smyk M, Cooper ML, Bader P, Cheung SW, Stankiewicz P. PTCH1 duplication in a family with microcephaly and mild developmental delay. Eur J Hum Genet. 2009;17(2):267‐271
  7.  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
  8.  Ribeiro LA, Murray JC, Richieri-Costa A. PTCH mutations in four Brazilian patients with holoprosencephaly and in one with holoprosencephaly-like features and normal MRI. Am J Med Genet A. 2006;140(23):2584‐2586

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Updated on November 30, 2020
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