Pseudodominant Nanophthalmos in a Roma Family Caused by a Novel PRSS56 Variant
Background. The aim of the study was to identify the molecular genetic cause of two different Mendelian traits with ocular involvement present in the members of a single consanguineous Czech Roma family. Methods. We have performed ocular examination and review of medical records in two individuals d...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Ophthalmology |
| Online Access: | http://dx.doi.org/10.1155/2020/6807809 |
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| author | Lubica Dudakova Pavlina Skalicka Olga Ulmanová Martin Hlozanek Viktor Stranecky Frantisek Malinka Andrea L. Vincent Petra Liskova |
| author_facet | Lubica Dudakova Pavlina Skalicka Olga Ulmanová Martin Hlozanek Viktor Stranecky Frantisek Malinka Andrea L. Vincent Petra Liskova |
| author_sort | Lubica Dudakova |
| collection | DOAJ |
| description | Background. The aim of the study was to identify the molecular genetic cause of two different Mendelian traits with ocular involvement present in the members of a single consanguineous Czech Roma family. Methods. We have performed ocular examination and review of medical records in two individuals diagnosed with nanophthalmos (proband and her father) and one individual followed for bilateral congenital cataract and microcornea (uncle of the proband). DNA of subjects with nanophthalmos was analysed by exome sequencing. Sanger sequencing was applied for targeted screening of potentially pathogenic variants and to follow segregation of identified variants within the family. Results. A homozygous variant c.1509G>C; p.(Met503Ile), in PRSS56 was found in the two individuals affected with nanophthalmos. The change was absent from the gnomAD dataset, but two out of 118 control Roma individuals were also shown to be heterozygous carriers. Analysis of single nucleotide polymorphisms in linkage disequilibrium with the c.1509G>C in PRSS56 suggested a shared chromosomal segment. The nanophthalmos phenotype, characterized in detail in the younger individual, encompassed bilateral corneal steepening, retinal folds, buried optic head drusen, and restricted visual fields, but no signs of retinal dystrophy. A known pathogenic founder CTDP1 variant c.863+389C>T in a homozygous state was identified in the other family member confirming the suspected diagnosis of congenital cataracts, facial dysmorphism, and demyelinating neuropathy syndrome. Conclusions. Herein, we report the first occurrence of nanophthalmos in the Roma population. We have identified pseudodominant inheritance for this phenotype caused by a novel variant in PRSS56, representing a possible founder effect. Despite advances in genetic technologies such as exome sequencing, careful phenotype evaluation in patients from an isolated population, along with an awareness of population-specific founder effects, is necessary to ensure that accurate molecular diagnoses are made. |
| format | Article |
| id | doaj-art-a9f5bf8ee86445b5839f539bb8755dd6 |
| institution | Kabale University |
| issn | 2090-004X 2090-0058 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Ophthalmology |
| spelling | doaj-art-a9f5bf8ee86445b5839f539bb8755dd62025-02-03T06:05:14ZengWileyJournal of Ophthalmology2090-004X2090-00582020-01-01202010.1155/2020/68078096807809Pseudodominant Nanophthalmos in a Roma Family Caused by a Novel PRSS56 VariantLubica Dudakova0Pavlina Skalicka1Olga Ulmanová2Martin Hlozanek3Viktor Stranecky4Frantisek Malinka5Andrea L. Vincent6Petra Liskova7Research Unit for Rare Diseases, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 128 08 Prague, Czech RepublicResearch Unit for Rare Diseases, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 128 08 Prague, Czech RepublicDepartment of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Katerinska 30, 120 00 Prague, Czech RepublicDepartment of Ophthalmology, Second Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 150 06 Prague, Czech RepublicResearch Unit for Rare Diseases, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 128 08 Prague, Czech RepublicResearch Unit for Rare Diseases, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 128 08 Prague, Czech RepublicDepartment of Ophthalmology, New Zealand National Eye Centre, University of Auckland, Private Bag 92019, Auckland 1142, New ZealandResearch Unit for Rare Diseases, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 128 08 Prague, Czech RepublicBackground. The aim of the study was to identify the molecular genetic cause of two different Mendelian traits with ocular involvement present in the members of a single consanguineous Czech Roma family. Methods. We have performed ocular examination and review of medical records in two individuals diagnosed with nanophthalmos (proband and her father) and one individual followed for bilateral congenital cataract and microcornea (uncle of the proband). DNA of subjects with nanophthalmos was analysed by exome sequencing. Sanger sequencing was applied for targeted screening of potentially pathogenic variants and to follow segregation of identified variants within the family. Results. A homozygous variant c.1509G>C; p.(Met503Ile), in PRSS56 was found in the two individuals affected with nanophthalmos. The change was absent from the gnomAD dataset, but two out of 118 control Roma individuals were also shown to be heterozygous carriers. Analysis of single nucleotide polymorphisms in linkage disequilibrium with the c.1509G>C in PRSS56 suggested a shared chromosomal segment. The nanophthalmos phenotype, characterized in detail in the younger individual, encompassed bilateral corneal steepening, retinal folds, buried optic head drusen, and restricted visual fields, but no signs of retinal dystrophy. A known pathogenic founder CTDP1 variant c.863+389C>T in a homozygous state was identified in the other family member confirming the suspected diagnosis of congenital cataracts, facial dysmorphism, and demyelinating neuropathy syndrome. Conclusions. Herein, we report the first occurrence of nanophthalmos in the Roma population. We have identified pseudodominant inheritance for this phenotype caused by a novel variant in PRSS56, representing a possible founder effect. Despite advances in genetic technologies such as exome sequencing, careful phenotype evaluation in patients from an isolated population, along with an awareness of population-specific founder effects, is necessary to ensure that accurate molecular diagnoses are made.http://dx.doi.org/10.1155/2020/6807809 |
| spellingShingle | Lubica Dudakova Pavlina Skalicka Olga Ulmanová Martin Hlozanek Viktor Stranecky Frantisek Malinka Andrea L. Vincent Petra Liskova Pseudodominant Nanophthalmos in a Roma Family Caused by a Novel PRSS56 Variant Journal of Ophthalmology |
| title | Pseudodominant Nanophthalmos in a Roma Family Caused by a Novel PRSS56 Variant |
| title_full | Pseudodominant Nanophthalmos in a Roma Family Caused by a Novel PRSS56 Variant |
| title_fullStr | Pseudodominant Nanophthalmos in a Roma Family Caused by a Novel PRSS56 Variant |
| title_full_unstemmed | Pseudodominant Nanophthalmos in a Roma Family Caused by a Novel PRSS56 Variant |
| title_short | Pseudodominant Nanophthalmos in a Roma Family Caused by a Novel PRSS56 Variant |
| title_sort | pseudodominant nanophthalmos in a roma family caused by a novel prss56 variant |
| url | http://dx.doi.org/10.1155/2020/6807809 |
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