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Japanese Journal of Ophthalmology
Published in: Japanese Journal of Ophthalmology 2/2020

01-03-2020 | Electroencephalography | Laboratory Investigation

Two sisters with microphthalmia and anterior segment dysgenesis secondary to a PAX6 pathogenic variant with clinically healthy parents: a case of gonadal mosaicism?

Authors: Anna Wawrocka, Joanna Walczak-Sztulpa, Ewelina Bukowska-Olech, Aleksander Jamsheer, Marcin Jaworski, Piotr Jaworski, Maciej Robert Krawczynski

Published in: Japanese Journal of Ophthalmology | Issue 2/2020

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Abstract

Purpose

Genetic analysis of two siblings with complex microphthalmia, with clinically healthy parents.

Study design

Clinical and experimental.

Methods

The patients underwent a detailed ophthalmic evaluation, including visual acuity, fundus examination, gonioscopy, ultrasound examination, and optical coherence tomography. Lensectomy with anterior vitrectomy was conducted in both patients. Additionally, in patient p1, electroencephalography analysis was performed. Genetic analysis was carried out using array comparative genomic hybridization (aCGH) and whole exome sequencing (WES). Bidirectional Sanger sequencing was conducted for validation and segregation analysis of the identified variant in the family.

Results

The aCGH results were normal. The heterozygous PAX6 variant c.52G>C (p.Gly18Arg) was identified in the proband (p1) through WES analysis. Sanger sequencing of exon 5 of PAX6 confirmed the presence of the variant in the other affected sibling (patient p2) but did not allow for identification of the variant in the parents’ DNA isolated from leukocytes and buccal cells.

Conclusions

The description of the variant in PAX6 in two siblings with clinically healthy parents who are negative for the mutation in DNA from leukocytes and buccal cells represents the possibility of parental gonadal mosaicism. Detection of germ cell mosaicism in the parents is essential to provide genetic counseling to the family regarding the risk of reoccurrence. Furthermore, we also report a pathogenic variant in PAX6 that to our knowledge has not so far been reported in patients with partial aniridia and therefore broadens the spectrum of the variants associated with aniridia.
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Metadata
Title
Two sisters with microphthalmia and anterior segment dysgenesis secondary to a PAX6 pathogenic variant with clinically healthy parents: a case of gonadal mosaicism?
Authors
Anna Wawrocka
Joanna Walczak-Sztulpa
Ewelina Bukowska-Olech
Aleksander Jamsheer
Marcin Jaworski
Piotr Jaworski
Maciej Robert Krawczynski
Publication date
01-03-2020
Publisher
Springer Japan
Published in
Japanese Journal of Ophthalmology / Issue 2/2020
Print ISSN: 0021-5155
Electronic ISSN: 1613-2246
DOI
https://doi.org/10.1007/s10384-020-00715-6

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