Abstract
Purpose
To investigate a very rare case of hypotrichosis with cone-rod dystrophy caused by a P-cadherin CDH3 mutation.
Methods
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.
Results
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).
Conclusion
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.
References
Hull S, Arno G, Robson AG et al (2016) Characterization of CDH3-related congenital hypotrichosis with juvenile macular dystrophy. JAMA Ophthalmol 134:992–1000. https://doi.org/10.1001/jamaophthalmol.2016.2089
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. https://doi.org/10.1016/j.ajoc.2017.06.007
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. https://doi.org/10.1038/ng716
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. https://doi.org/10.1159/000327156
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. https://doi.org/10.1007/s10633-014-9473-7
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. https://doi.org/10.1007/s10633-015-9504-z
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. https://doi.org/10.1038/ejhg.2013.72
Weisschuh N, Mayer AK, Strom TM et al (2016) Mutation detection in patients with retinal dystrophies using targeted next generation sequencing. PLoS One. https://doi.org/10.1371/journal.pone.0145951
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. https://doi.org/10.1046/j.1523-1747.2003.12550_1.x
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. https://doi.org/10.1046/j.1523-1747.2002.19528.x
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. https://doi.org/10.1111/j.1365-2230.2008.02933.x
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. https://doi.org/10.1007/s00403-010-1035-6
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. https://doi.org/10.1046/j.1523-1747.2002.19528.x
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. https://doi.org/10.1046/j.1523-1747.2003.12550_1.x
Leibu R, Jermans A, Hatim G et al (2006) Hypotrichosis with juvenile macular dystrophy. Ophthalmology 113:841–847.e3. https://doi.org/10.1016/j.ophtha.2005.10.065
Khan AO, Bolz HJ (2016) Phenotypic observations in “hypotrichosis with juvenile macular dystrophy” (recessive CDH3 mutations). Ophthalmic Genet 37:301–306. https://doi.org/10.3109/13816810.2015.1071411
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. https://doi.org/10.1083/jcb.109.4.1787
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. https://doi.org/10.1006/exer.2002.1175
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. https://doi.org/10.1111/j.1600-0625.1999.tb00377.x
Goodwin M, Yap AS (2004) Classical cadherin adhesion molecules: coordinating cell adhesion, signaling and the cytoskeleton. J Mol Histol 35:839–844. https://doi.org/10.1007/s10735-004-1833-2
Acknowledgements
We thank Dr. Anne Kurtenbach for her critical reading of the manuscript and Dr. Torsten Strasser for his help with the ERG analysis.
Funding
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.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
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.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Nasser, F., Mulahasanovic, L., Alkhateeb, M. et al. Hypotrichosis with cone-rod dystrophy in a patient with cadherin 3 (CDH3) mutation. Doc Ophthalmol 138, 153–160 (2019). https://doi.org/10.1007/s10633-019-09675-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10633-019-09675-w