Hypotrichosis with cone-rod dystrophy in a patient with cadherin 3 (CDH3) mutation

  • F. NasserEmail author
  • L. Mulahasanovic
  • M. Alkhateeb
  • S. Biskup
  • K. Stingl
  • E. Zrenner
Clinical Case Report



To investigate a very rare case of hypotrichosis with cone-rod dystrophy caused by a P-cadherin CDH3 mutation.


A 16-year-old Syrian girl was examined at age 9 and 14 years with an ophthalmological examination, fundus imaging, OCT and electrophysiological recordings (ERG and PERG). A disease-targeted gene panel sequencing was performed.


Fundus images showed pigmentations at the posterior eye pole to the mid periphery, as well as vessel tortuosity. OCT images revealed a loss of the outer retinal segments and IS/OS in the central macula. The scotopic and photopic ERGs showed moderately reduced amplitudes at age 9 years that became severely reduced at age of 14 years. The PERG was undetectable at age 9 years. In color vision testing, protan–deutan confusion errors occurred. Gene panel analysis revealed one homozygous mutation in CDH3 (c.1508G>A; p.Arg503His).


This case shows that a CDH3 mutation besides macula dystrophy can cause widespread cone-rod dystrophy with hypotrichosis without any other pathology besides hypoplastic nails. This points to a common pathway of hair growth and photoreceptor development that can be disturbed by a CDH3 mutation (c.1508G>A; p.Arg503His) located in the EC4 repeat region of the gene.


Hypotrichosis Electroretinography Cone-rod dystrophy CDH3 



We thank Dr. Anne Kurtenbach for her critical reading of the manuscript and Dr. Torsten Strasser for his help with the ERG analysis.


The study was supported by grants from the German Research Council (DFG Excellence Center EXC307) to EZ, and from the Tistou and Charlotte Kerstan Foundation to FN.

Compliance with ethical standards

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Statements of human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Statement on the welfare of animals

This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from both parents of the participant included in the study.


  1. 1.
    Hull S, Arno G, Robson AG et al (2016) Characterization of CDH3-related congenital hypotrichosis with juvenile macular dystrophy. JAMA Ophthalmol 134:992–1000. CrossRefGoogle Scholar
  2. 2.
    Karti O, Abali S, Ayhan Z et al (2017) CDH3 gene related hypotrichosis and juvenile macular dystrophy—a case with a novel mutation. Am J Ophthalmol Case Rep 7:129–133. CrossRefGoogle Scholar
  3. 3.
    Sprecher E, Bergman R, Richard G et al (2001) Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin. Nat Genet 29:134–136. CrossRefGoogle Scholar
  4. 4.
    Basel-Vanagaite L, Pasmanik-Chor M, Lurie R et al (2010) CDH3-related syndromes: report on a new mutation and overview of the genotype–phenotype correlations. Mol Syndromol 1:223–230. CrossRefGoogle Scholar
  5. 5.
    McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R, Bach M (2015) ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130(1):1–12. CrossRefGoogle Scholar
  6. 6.
    McCulloch DL, Marmor MF, Brigell MG et al (2015) Erratum to: ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 131:81–83. CrossRefGoogle Scholar
  7. 7.
    Glöckle N, Kohl S, Mohr J et al (2014) Panel-based next generation sequencing as a reliable and efficient technique to detect mutations in unselected patients with retinal dystrophies. Eur J Hum Genet 22:99–104. CrossRefGoogle Scholar
  8. 8.
    Weisschuh N, Mayer AK, Strom TM et al (2016) Mutation detection in patients with retinal dystrophies using targeted next generation sequencing. PLoS One. Google Scholar
  9. 9.
    Indelman M, Bergman R, Ramon M et al (2003) Phenotypic diversity and mutation spectrum in hypotrichosis with juvenile macular dystrophy. J Invest Dermatol 121:1217–1220. CrossRefGoogle Scholar
  10. 10.
    Indelman M, Bergman R, Petronius D et al (2002) A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy. J Invest Dermatol 119:1210–1213. CrossRefGoogle Scholar
  11. 11.
    Jelani M, Salman Chishti M, Ahmad W (2009) A novel splice-site mutation in the CDH3 gene in hypotrichosis with juvenile macular dystrophy. Clin Exp Dermatol 34:68–73. CrossRefGoogle Scholar
  12. 12.
    Kamran-ul-Hassan Naqvi S, Azeem Z, Ali G, Ahmad W (2010) A novel splice-acceptor site mutation in CDH3 gene in a consanguineous family exhibiting hypotrichosis with juvenile macular dystrophy. Arch Dermatol Res 302:701–703. CrossRefGoogle Scholar
  13. 13.
    Indelman M, Bergman R, Lurie R, Richard G, Miller B, Petronius D, Ciubutaro D, Leibu R, Sprecher E (2002) A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy. J Invest Dermatol 119(5):1210–1213. CrossRefGoogle Scholar
  14. 14.
    Indelman M, Hamel CP, Bergman R, Nischal KK, Thompson D, Surget MO, Ramon M, Ganthos H, Miller B, Richard G, Lurie R, Leibu R, Russell-Eggitt I, Sprecher E (2003) Phenotypic diversity and mutation spectrum in hypotrichosis with juvenile macular dystrophy. J Invest Dermatol 121(5):1217–1220. CrossRefGoogle Scholar
  15. 15.
    Leibu R, Jermans A, Hatim G et al (2006) Hypotrichosis with juvenile macular dystrophy. Ophthalmology 113:841–847.e3. CrossRefGoogle Scholar
  16. 16.
    Khan AO, Bolz HJ (2016) Phenotypic observations in “hypotrichosis with juvenile macular dystrophy” (recessive CDH3 mutations). Ophthalmic Genet 37:301–306. CrossRefGoogle Scholar
  17. 17.
    Shimoyama Y, Yoshida T, Terada M et al (1989) Molecular cloning of a human Ca2+-dependent cell-cell adhesion molecule homologous to mouse placental cadherin: Its low expression in human placental tissues. J Cell Biol 109:1787–1794. CrossRefGoogle Scholar
  18. 18.
    Xu L, Overbeek PA, Reneker LW (2002) Systematic analysis of E-, N- and P-cadherin expression in mouse eye development. Exp Eye Res 74:753–760. CrossRefGoogle Scholar
  19. 19.
    Müller-Röver S, Tokura Y, Welker P et al (2007) E- and P-cadherin expression during murine hair follicle morphogenesis and cycling. Exp Dermatol 8:237–246. CrossRefGoogle Scholar
  20. 20.
    Goodwin M, Yap AS (2004) Classical cadherin adhesion molecules: coordinating cell adhesion, signaling and the cytoskeleton. J Mol Histol 35:839–844. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute for Ophthalmic Research, Centre for OphthalmologyUniversity of TuebingenTübingenGermany
  2. 2.Praxis for Human GeneticsTübingenGermany
  3. 3.CeGaT GmbHTübingenGermany
  4. 4.Eye and Ear Specialty HospitalDamascusSyria
  5. 5.Werner Reichardt Center for Integrative Neuroscience (CIN)University of TuebingenTübingenGermany

Personalised recommendations