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Progressive retinal degeneration in a girl with Knobloch syndrome who presented with signs of ocular albinism

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Abstract

Purpose

We report for the first time electroretinographic (ERG) evidence of progressive retinal abnormalities in a girl who presented in infancy with ocular features of albinism and gradually developed choroidal sclerosis and patchy retinal atrophy leading to a diagnosis of Knobloch syndrome (KS, OMIM 267750, COL18A1).

Methods

At age 2 months, nystagmus and esotropia prompted ophthalmic evaluation. The appearance of choroidal sclerosis and atrophic retinal patches led to further evaluation at age 8 years. Genetics consultation was obtained in infancy and again at age 8 years as retinal findings evolved. Full field ERG responses in both scotopic and photopic conditions were recorded at both ages and compared to those in healthy control subjects.

Results

At age 2 months ERG response parameters were within normal limits for age and tyrosinase (TYR) gene sequencing revealed one novel mutation, p.S466F, and the temperature-sensitive polymorphism, p.R402Q, suggesting the diagnosis of oculocutaneous albinism type 1 (OCA1). At age 8 years, there was significant attenuation of both scotopic and photopic ERG responses. Genetic re-analysis led to the identification of a homozygous mutation, c.3213dupC, in the COL18A1 gene, thus confirming the diagnosis of Knobloch syndrome.

Conclusions

Our patient with Knobloch syndrome developed abnormal ERG responses similar to those found in col18a1 knockout mice. Thus, we have documented progressive attenuation of the scotopic and photopic responses in KS.

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Authors and Affiliations

  1. Department of Ophthalmology, Soroka Medical Center and Clalit Health Services, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel

    Libe Gradstein

  2. Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Ave., Boston, MA, 02115-5737, USA

    Ronald M. Hansen, Pablo Altschwager & Anne B. Fulton

  3. Division of Genetics and Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Gerald F. Cox

  4. Editas Medicine, 11 Hurley St., Cambridge, 02141, MA, USA

    Gerald F. Cox

  5. Department of Ophthalmology, Pontificia Universidad Catolica de Chile, Santiago, Chile

    Pablo Altschwager

Authors
  1. Libe Gradstein
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  2. Ronald M. Hansen
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  3. Gerald F. Cox
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  4. Pablo Altschwager
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  5. Anne B. Fulton
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Corresponding author

Correspondence to Anne B. Fulton.

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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.

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Ethical approval 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 Helsinki Declaration and its later amendments or comparable ethical standards.

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

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Informed consent was obtained from all individual participants included in the study.

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Gradstein, L., Hansen, R.M., Cox, G.F. et al. Progressive retinal degeneration in a girl with Knobloch syndrome who presented with signs of ocular albinism. Doc Ophthalmol 134, 135–140 (2017). https://doi.org/10.1007/s10633-017-9574-1

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  • DOI: https://doi.org/10.1007/s10633-017-9574-1

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