Screening of West Siberian patients with primary congenital glaucoma for CYP1B1 gene mutations
Primary congenital glaucoma (PСG) is a visual organ pathology that leads to progressive blindness and poor vision in children. Its main cause is an anomaly of the anterior chamber angle. Most cases of PСG are sporadic, but familial cases with an autosomal recessive (predominantly) and autosomal domi...
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2020-12-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/2846 |
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| author | D. E. Ivanoshchuk S. V. Mikhailova O. G. Fenkova E. V. Shakhtshneider A. Z. Fursova I. V. Bychkov M. I. Voevoda |
| author_facet | D. E. Ivanoshchuk S. V. Mikhailova O. G. Fenkova E. V. Shakhtshneider A. Z. Fursova I. V. Bychkov M. I. Voevoda |
| author_sort | D. E. Ivanoshchuk |
| collection | DOAJ |
| description | Primary congenital glaucoma (PСG) is a visual organ pathology that leads to progressive blindness and poor vision in children. Its main cause is an anomaly of the anterior chamber angle. Most cases of PСG are sporadic, but familial cases with an autosomal recessive (predominantly) and autosomal dominant (rare) type of inheritance have been described. Congenital glaucoma is a rare condition (1 case per 10,000–20,000 newborns), but its prevalence is substantially higher (up to 1 case per 250 newborns) in countries where consanguineous marriages are common. Mutations in the CYP1B1 gene, which encodes cytochrome P450 1B1, are the most common cause of autosomal recessive primary congenital glaucoma. This enzyme is known to be involved in retinoic acid metabolism and is necessary for normal eye development. The aim of this work was to assess the polymorphism of the CYP1B1 gene among West Siberian patients with primary congenital glaucoma. Direct automatic Sanger sequencing of exons and adjacent splicing sites of the CYP1B1 gene was carried out in 28 people with the PCG phenotype from a West Siberian region. As a result, in the sample of the white population we examined, pathogenic variants previously described in other ethnic groups were revealed: E387K (rs55989760), R444* (rs377049098), R444Q (rs72549376), and P437L (rs56175199), as well as novel single-nucleotide deletion p.F114Lfs*38 in the CYP1B1 gene. The latter can cause a frame shift, changed amino acid composition, and a formation of truncated in the protein. None of the detected mutations were found in the control sample of ophthalmologically examined individuals without PCG (100 people). Variants R444* (rs377049098) and R444Q (rs72549376) were not found in the general population sample either (576 randomly selected West Siberia residents). All the detected mutations caused the development of the autosomal recessive form of primary congenital glaucoma. The most severe clinical phenotype was observed in carriers of mutations in codon 444 of the gene. Consequently, in children with signs of increased intraocular pressure, molecular genetic analysis of the CYP1B1 gene is advisable for early diagnosis and timely initiation of PCG therapy. |
| format | Article |
| id | doaj-art-dcf618ea9be5493a9bb9c336173aefee |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2020-12-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-dcf618ea9be5493a9bb9c336173aefee2025-02-01T09:58:09ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592020-12-0124886186710.18699/VJ20.6841116Screening of West Siberian patients with primary congenital glaucoma for CYP1B1 gene mutationsD. E. Ivanoshchuk0S. V. Mikhailova1O. G. Fenkova2E. V. Shakhtshneider3A. Z. Fursova4I. V. Bychkov5M. I. Voevoda6Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesNovosibirsk State Regional HospitalInstitute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesS.N. Fyodorov FSBI IRTC Eye Microsurgery, Novosibirsk branchInstitute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesPrimary congenital glaucoma (PСG) is a visual organ pathology that leads to progressive blindness and poor vision in children. Its main cause is an anomaly of the anterior chamber angle. Most cases of PСG are sporadic, but familial cases with an autosomal recessive (predominantly) and autosomal dominant (rare) type of inheritance have been described. Congenital glaucoma is a rare condition (1 case per 10,000–20,000 newborns), but its prevalence is substantially higher (up to 1 case per 250 newborns) in countries where consanguineous marriages are common. Mutations in the CYP1B1 gene, which encodes cytochrome P450 1B1, are the most common cause of autosomal recessive primary congenital glaucoma. This enzyme is known to be involved in retinoic acid metabolism and is necessary for normal eye development. The aim of this work was to assess the polymorphism of the CYP1B1 gene among West Siberian patients with primary congenital glaucoma. Direct automatic Sanger sequencing of exons and adjacent splicing sites of the CYP1B1 gene was carried out in 28 people with the PCG phenotype from a West Siberian region. As a result, in the sample of the white population we examined, pathogenic variants previously described in other ethnic groups were revealed: E387K (rs55989760), R444* (rs377049098), R444Q (rs72549376), and P437L (rs56175199), as well as novel single-nucleotide deletion p.F114Lfs*38 in the CYP1B1 gene. The latter can cause a frame shift, changed amino acid composition, and a formation of truncated in the protein. None of the detected mutations were found in the control sample of ophthalmologically examined individuals without PCG (100 people). Variants R444* (rs377049098) and R444Q (rs72549376) were not found in the general population sample either (576 randomly selected West Siberia residents). All the detected mutations caused the development of the autosomal recessive form of primary congenital glaucoma. The most severe clinical phenotype was observed in carriers of mutations in codon 444 of the gene. Consequently, in children with signs of increased intraocular pressure, molecular genetic analysis of the CYP1B1 gene is advisable for early diagnosis and timely initiation of PCG therapy.https://vavilov.elpub.ru/jour/article/view/2846humancongenital glaucomacyp1b1genetic analysiscytochrome p450 1b1 |
| spellingShingle | D. E. Ivanoshchuk S. V. Mikhailova O. G. Fenkova E. V. Shakhtshneider A. Z. Fursova I. V. Bychkov M. I. Voevoda Screening of West Siberian patients with primary congenital glaucoma for CYP1B1 gene mutations Вавиловский журнал генетики и селекции human congenital glaucoma cyp1b1 genetic analysis cytochrome p450 1b1 |
| title | Screening of West Siberian patients with primary congenital glaucoma for CYP1B1 gene mutations |
| title_full | Screening of West Siberian patients with primary congenital glaucoma for CYP1B1 gene mutations |
| title_fullStr | Screening of West Siberian patients with primary congenital glaucoma for CYP1B1 gene mutations |
| title_full_unstemmed | Screening of West Siberian patients with primary congenital glaucoma for CYP1B1 gene mutations |
| title_short | Screening of West Siberian patients with primary congenital glaucoma for CYP1B1 gene mutations |
| title_sort | screening of west siberian patients with primary congenital glaucoma for cyp1b1 gene mutations |
| topic | human congenital glaucoma cyp1b1 genetic analysis cytochrome p450 1b1 |
| url | https://vavilov.elpub.ru/jour/article/view/2846 |
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