Clinical analysis of a family with Wagner syndrome_Chinese Journal of Ocular Fundus Diseases

Authors：

 Hu Yuzhang

Chengdu Aidi Eye Hospital, Chengdu 610072, China;

Corresponding?author：

Hu Yuzhang, Email: rsn2008@sina.com

Keywords：

Wagner syndrome; VCAN gene; Chorioretinal atrophy; Cataracts; Vitreous proliferative

DOI：

10.3760/cma.j.cn511434-20240117-00035

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To observe the clinical manifestations of a Wagner syndrome (WS) family. Methods A retrospective clinical study. Four patients (the proband, his father, sister, and brother) and one family member (the proband's mother) from a WS family diagnosed by clinical examination in Chengdu Aidi Eye Hospital in June 2023 were included in the study. The proband's medical history was examined in detail, followed by best corrected visual acuity (BCVA), fundus color photography, optical coherence tomography (OCT), and OCT angiography (OCTA). The proband underwent full field electroretinogram (ERG) examination. The proband and his sister and brother underwent blood glucose, blood pressure, hearing, face, joint, exercise and general physical examination at the same time. Peripheral venous blood was collected from the proband and 4 other family members. The proband extracts genomic DNA samples, conducts target region capture, library construction and high-throughput sequencing after qualified quality control. The suspected pathogenic mutation sites were verified by Sanger. According to the selected mutation sites, other family members in this family were co-isolated and verified. The pathogenicity of the mutation site was analyzed using the guidelines of the American College of Medical Genetics and Genomics (ACMG). Results Proband (Ⅱ-1) was 23 years old female. Both eyes BCVA were 0.1. The waveforms of ERG in both eyes were basically normal, and some amplitudes were reduced. Sister of the proband (Ⅱ-2) was 20 years old. Both eyes BCVA 1.0. Fundus examination showed no obvious abnormality. Brother of the proband (Ⅱ-3) was 19 years old. The left eye underwent pars plana vitrectomy combined with silicone oil filling 2 years ago due to retinal detachment and severe vitreous hyperplasia. BCVA light sensitivity, complicated cataract, and fundus opacity were observed. Right eye BCVA was 0.1. The lenses of the proband and his younger sister and brother were pointed and wedged, and the younger brother was heavier. Vitreous cavity of lens. The retina color of both eyes and the right eye of the younger brother of the protor was dark, with flaky dark areas on the side of the nose and the posterior pole, and the symmetrical retinal veil membrane hyperplasia and pulling on the periphery, showing small retinal splits. The choroidal retina showed focal and segmental symmetrically large atrophy. The optic disc was tilted. By OCT examination, the ellipsoid band was partially missing and broken, and the thickness of the choroid layer was reduced. Retinal cortical atrophy in 1 eye (younger brother of proband). By OCTA examination, the mesovascular layer of choroid was atrophied seriously and the blood density decreased. The results of laboratory and general examination of the three siblings showed no obvious abnormalities. The results of genetic testing showed that the proband, his father (Ⅱ-1), his sister and his brother carried a heterozygous mutation of the VCAN gene c.9264A>G (p.Pro3088=). According to ACMG guidelines, the pathogenicity of this variant was unknown. The mother of proband (Ⅰ-2) was wild type. Conclusions The abnormal manifestations of WS eyes are diverse, and both anterior and posterior segments could be involved. The pathogenicity of the heterozygous variation of VCAN gene c.9264A>G (P.RO3088 =) in this family is unknown.

Citation： Hu Yuzhang. Clinical analysis of a family with Wagner syndrome. Chinese Journal of Ocular Fundus Diseases, 2024, 40(10): 766-771. doi: 10.3760/cma.j.cn511434-20240117-00035 Copy

1.	蔡素萍, 張達人, 羅小玲, 等. 中國漢族Wagner綜合征一家系臨床與分子遺傳學研究[J]. 中華實驗眼科雜志, 2022, 40(10): 914-919. DOI: 10.3760/cma.j.cn115989-20210318-00184.Cai SP, Zhang DR, Luo XL, et al. A study on the clinical and molecular genetics of Wagner syndrome in a Chinese Han family[J]. Chin J Exp Ophthalmol, 2022, 40(10): 914-919. DOI: 10.3760/cma.j.cn115989-20210318-00184.
2.	Thomas AS, Branham K, Van Gelder RN, et al. Multimodal imaging in Wagner syndrome[J]. Ophthalmic Surg Lasers Imaging Retina, 2016, 47(6): 574-579. DOI: 10.3928/23258160-20160601-10.
3.	Araújo JR, Tavares-Ferreira J, Estrela-Silva S, et al. Wagner syndrome: anatomic, functional and genetic characterization of a Portuguese family[J]. Graefe's Arch Clin Exp Ophthalmol, 2018, 256(1): 163-171. DOI: 10.1007/s00417-017-3800-0.
4.	Acón D, Hussain RM, Yannuzzi NA, et al. Complex combined tractional and rhegmatogenous retinal detachment in a twenty three-year-old male with Wagner syndrome[J]. Ophthalmic Surg Lasers Imaging Retina, 2020, 51: 467-471. DOI: 10.3928/23258160-20200804-07.
5.	Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. DOI: 10.1038/gim.2015.30.
6.	王秋菊, 沈亦平, 陳少科, 等. 遺傳變異分類標準與指南[J]. 中國科學(生命科學), 2017, 47(6): 668-688. DOI: 10.1360/N052017-00099.Wang QJ, Shen YP, Chen SK, et al. Standards and guidelines for the interpretation of sequence variants[J]. Science in China (Life Sciences), 2017, 47(6): 668-688. DOI: 10.1360/N052017-00099.
7.	Miller DT, Lee K, Abul-Husn NS, et al. ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG)[J/OL]. Genet Med, 2023, 25(8): 100866[2023-06-22]. https://pubmed.ncbi.nlm.nih.gov/37347242/. DOI: 10.1016/j.gim.2023.100866.
8.	Wagner H. Ein bisher unbekanntes Erbleiden des Auges, beobachtet im Kanton Zurich 1[J]. Klin Monbl Augenheilkd, 1938, 100: 840-857.
9.	Bleicher ID, Garg I, Hoyek S, et al. Widefield swept-source optical coherence tomography angiography findings in Wagner syndrome[J]. Retin Cases Brief Rep, 2024, 18(1): 80-86. DOI: 10.1097/ICB.0000000000001307.
10.	Graeme Charles M. Wagner syndrome[M]//Puech B, De Laey JJ, Holder GE. Inherited chorioretinal dystrophies. Berlin: Springer, 2014: 417-420.
11.	Jewsbury H, Fry AE, Watts P, et al. Congenital glaucoma in Wagner syndrome[J]. J AAPOS, 2014, 18(3): 291-293. DOI: 10.1016/j.jaapos.2013.12.014.
12.	Rothschild PR, Brézin AP, Nedelec B, et al. A family with Wagner syndrome with uveitis and a new versican mutation[J]. Mol Vis, 2013, 19: 2040-2049.
13.	Trinh MV, Lee JG, Ferrone PJ. Stickler and Wagner syndrome in African Americans Ophthalmic[J]. Surg Lasers Imaging Retina, 2023, 54(2): 97-101. DOI: 10.3928/23258160-20221118-01.
14.	黃輝, 沈亦平, 顧衛紅, 等. 臨床基因檢測報告規范與基因檢測行業共識探討[J]. 中華醫學遺傳學雜志, 2018, 35(1): 1-8. DOI: 10.3760/cma.j.issn.1003-9406.2018.01.001.Huang H, Shen YP, Gu WH, et al. Discussion on the standard of clinical genetic testing report and the consensus of gene testing industry[J]. Chin J Med Genet, 2018, 35(1): 1-8. DOI: 10.3760/cma.j.issn.1003-9406.2018.01.001.
15.	Talevich E, Shain AH, Botton T, et al. CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing[J/OL]. PLoS Comput Biol, 2016, 12(4): e1004873[2016-04-21]. https://pubmed.ncbi.nlm.nih.gov/27100738/. DOI: 10.1371/journal.pcbi.1004873.
16.	Enriquez AB, Baumal GR. Genetic diseases causing RRD: Marfan, Stickler and Wagner syndrome[M]//?zdek ?, Berrocal A, Spandau U. Pediatric vitreoretinal surgery. Berlin: Springer, 2023: 473-492.
17.	Bernabei F, Brezin AP, Rothschild PR. Circumferential equatorial vitreous veil in a patient with Wagner syndrome[J]. J Fr Ophtalmol, 2022, 45(10): 1222-1223. DOI: 10.1016/j.jfo.2022.05.018.
18.	Sebes J. Wagner-Stickler syndrome[M]//Lang F. Encyclopedia of molecular mechanisms of disease[J]. Berlin: Springer, 2009: 2236.

1. 蔡素萍, 張達人, 羅小玲, 等. 中國漢族Wagner綜合征一家系臨床與分子遺傳學研究[J]. 中華實驗眼科雜志, 2022, 40(10): 914-919. DOI: 10.3760/cma.j.cn115989-20210318-00184.Cai SP, Zhang DR, Luo XL, et al. A study on the clinical and molecular genetics of Wagner syndrome in a Chinese Han family[J]. Chin J Exp Ophthalmol, 2022, 40(10): 914-919. DOI: 10.3760/cma.j.cn115989-20210318-00184.
2. Thomas AS, Branham K, Van Gelder RN, et al. Multimodal imaging in Wagner syndrome[J]. Ophthalmic Surg Lasers Imaging Retina, 2016, 47(6): 574-579. DOI: 10.3928/23258160-20160601-10.
3. Araújo JR, Tavares-Ferreira J, Estrela-Silva S, et al. Wagner syndrome: anatomic, functional and genetic characterization of a Portuguese family[J]. Graefe's Arch Clin Exp Ophthalmol, 2018, 256(1): 163-171. DOI: 10.1007/s00417-017-3800-0.
4. Acón D, Hussain RM, Yannuzzi NA, et al. Complex combined tractional and rhegmatogenous retinal detachment in a twenty three-year-old male with Wagner syndrome[J]. Ophthalmic Surg Lasers Imaging Retina, 2020, 51: 467-471. DOI: 10.3928/23258160-20200804-07.
5. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. DOI: 10.1038/gim.2015.30.
6. 王秋菊, 沈亦平, 陳少科, 等. 遺傳變異分類標準與指南[J]. 中國科學(生命科學), 2017, 47(6): 668-688. DOI: 10.1360/N052017-00099.Wang QJ, Shen YP, Chen SK, et al. Standards and guidelines for the interpretation of sequence variants[J]. Science in China (Life Sciences), 2017, 47(6): 668-688. DOI: 10.1360/N052017-00099.
7. Miller DT, Lee K, Abul-Husn NS, et al. ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG)[J/OL]. Genet Med, 2023, 25(8): 100866[2023-06-22]. https://pubmed.ncbi.nlm.nih.gov/37347242/. DOI: 10.1016/j.gim.2023.100866.
8. Wagner H. Ein bisher unbekanntes Erbleiden des Auges, beobachtet im Kanton Zurich 1[J]. Klin Monbl Augenheilkd, 1938, 100: 840-857.
9. Bleicher ID, Garg I, Hoyek S, et al. Widefield swept-source optical coherence tomography angiography findings in Wagner syndrome[J]. Retin Cases Brief Rep, 2024, 18(1): 80-86. DOI: 10.1097/ICB.0000000000001307.
10. Graeme Charles M. Wagner syndrome[M]//Puech B, De Laey JJ, Holder GE. Inherited chorioretinal dystrophies. Berlin: Springer, 2014: 417-420.
11. Jewsbury H, Fry AE, Watts P, et al. Congenital glaucoma in Wagner syndrome[J]. J AAPOS, 2014, 18(3): 291-293. DOI: 10.1016/j.jaapos.2013.12.014.
12. Rothschild PR, Brézin AP, Nedelec B, et al. A family with Wagner syndrome with uveitis and a new versican mutation[J]. Mol Vis, 2013, 19: 2040-2049.
13. Trinh MV, Lee JG, Ferrone PJ. Stickler and Wagner syndrome in African Americans Ophthalmic[J]. Surg Lasers Imaging Retina, 2023, 54(2): 97-101. DOI: 10.3928/23258160-20221118-01.
14. 黃輝, 沈亦平, 顧衛紅, 等. 臨床基因檢測報告規范與基因檢測行業共識探討[J]. 中華醫學遺傳學雜志, 2018, 35(1): 1-8. DOI: 10.3760/cma.j.issn.1003-9406.2018.01.001.Huang H, Shen YP, Gu WH, et al. Discussion on the standard of clinical genetic testing report and the consensus of gene testing industry[J]. Chin J Med Genet, 2018, 35(1): 1-8. DOI: 10.3760/cma.j.issn.1003-9406.2018.01.001.
15. Talevich E, Shain AH, Botton T, et al. CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing[J/OL]. PLoS Comput Biol, 2016, 12(4): e1004873[2016-04-21]. https://pubmed.ncbi.nlm.nih.gov/27100738/. DOI: 10.1371/journal.pcbi.1004873.
16. Enriquez AB, Baumal GR. Genetic diseases causing RRD: Marfan, Stickler and Wagner syndrome[M]//?zdek ?, Berrocal A, Spandau U. Pediatric vitreoretinal surgery. Berlin: Springer, 2023: 473-492.
17. Bernabei F, Brezin AP, Rothschild PR. Circumferential equatorial vitreous veil in a patient with Wagner syndrome[J]. J Fr Ophtalmol, 2022, 45(10): 1222-1223. DOI: 10.1016/j.jfo.2022.05.018.
18. Sebes J. Wagner-Stickler syndrome[M]//Lang F. Encyclopedia of molecular mechanisms of disease[J]. Berlin: Springer, 2009: 2236.

Chinese Journal of Ocular Fundus Diseases

Clinical analysis of a family with Wagner syndrome

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content