July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Molecular genetic investigation of two distinct monogenic disorders with ocular involvement in a large consanguineous Roma family
Author Affiliations & Notes
  • Lubica Dudakova
    Charles University, Prague, Czechia
  • Pavlina Skalicka
    Charles University, Prague, Czechia
  • Petra Liskova
    Charles University, Prague, Czechia
  • Footnotes
    Commercial Relationships   Lubica Dudakova, None; Pavlina Skalicka, None; Petra Liskova, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 328. doi:
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      Lubica Dudakova, Pavlina Skalicka, Petra Liskova; Molecular genetic investigation of two distinct monogenic disorders with ocular involvement in a large consanguineous Roma family. Invest. Ophthalmol. Vis. Sci. 2018;59(9):328.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : The aim of our study was to identify the molecular genetic cause of two distinct disorders with ocular involvement in individuals from a consanguineous Roma family.

Methods : Ophthalmic examination and DNA extraction was performed in one family member with a history of bilateral congenital cataract, microcornea and neurological impairment, two members (parent and offspring) with nanophthalmos and two unaffected first degree relatives. Next, based on careful phenotype evaluation, an intronic region of CTDP1 was directly sequenced in the subject with congenital cataracts. Whole exome sequencing (WES) using Agilent SureSelect HumanXT Kit was performed in one individual with nanophthalmos and detected variants were evaluated for pathogenicity. Verification of the identified mutations and segregation analysis was performed using direct sequencing.

Results : A known homozygous mutation c.863+389C>T in CTDP1 was identified in an 30 year old male confirming the diagnosis of multi-systemic disorder CCFDN (Congenital Cataract Facial Dysmorphism and Demyelinating Neuropathy). A novel, potentially pathogenic, homozygous variant, c.1509G>C; p.(Met503Ile), was detected in PRSS56 by WES in a 15 year of niece of the CCFDN patient. Segregation analysis demonstrated that her father and mother were homozygous and heterozygous carriers of the same PRSS56 variant, respectively. The extended family were also reported to have a history of congenital deafness and severe visual and neurological impairment variably associated with mental retardation.

Conclusions : Despite advances in genetic sequencing technologies such as WES, careful phenotyping in combination with awareness of population specific founder effects are necessary to ensure that accurate molecular diagnoses are made. We have identified pseudodominant inheritance nanophthlamos, the first report of this phenotype in the Roma population.

Acknowledgements: This work was supported by UNCE 204011, PROGRES-Q26/LF1 and by AZV 17-30500A. PS was supported by GAUK 364/2017 and SVV 260367/2017. We thank The National Center for Medical Genomics (LM2015091) for providing ethnically matched population genotype frequency data (project CZ.02.1.01/0.0/0.0/16_013/0001634).

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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