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Homozygous Type IX collagen variants (COL9A1, COL9A2, and COL9A3) causing recessive Stickler syndrome-Expanding the phenotype.
Am J Med Genet A. 2019 08; 179(8):1498-1506.AJ

Abstract

Stickler syndrome (SS) is characterized by ophthalmic, articular, orofacial, and auditory manifestations. SS is usually autosomal dominantly inherited with variants in COL2A1 or COL11A1. Recessive forms are rare but have been described with homozygous variants in COL9A1, COL9A2, and COL9A3 and compound heterozygous COL11A1 variants. This article expands phenotypic descriptions in recessive SS due to variants in genes encoding Type IX collagen. Clinical features were assessed in four families. Genomic DNA samples derived from venous blood were collected from family members. Six affected patients were identified from four pedigrees with variants in COL9A1 (one family, one patient), COL9A2 (two families, three patients), and COL9A3 (one family, two patients). Three variants were novel. All patients were highly myopic with congenital megalophthalmos and abnormal, hypoplastic vitreous gel, and all had sensorineural hearing loss. One patient had severe arthropathy. Congenital megalophthalmos and myopia are common to dominant and recessive forms of SS. Sensorineural hearing loss is more common and severe in recessive SS. We suggest that COL9A1, COL9A2, and COL9A3 be added to genetic screening panels for patients with congenital hearing loss. Although recessive SS is rare, early diagnosis would have a high impact for children with potentially dual sensory impairment, as well as identifying risk to future children.

Authors+Show Affiliations

School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. Vitreoretinal Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. Vitreoretinal Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.Department of Pathology, University of Cambridge, Cambridge, UK.Department of Pathology, University of Cambridge, Cambridge, UK.Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.North West Thames Regional Genetic Services, Northwick Park Hospitals NHS Foundation Trust, London, UK. Department of Pediatrics, Emma Children's Hospital, Amsterdam, The Netherlands.School of Clinical Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. Vitreoretinal Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31090205

Citation

Nixon, Thomas R W., et al. "Homozygous Type IX Collagen Variants (COL9A1, COL9A2, and COL9A3) Causing Recessive Stickler syndrome-Expanding the Phenotype." American Journal of Medical Genetics. Part A, vol. 179, no. 8, 2019, pp. 1498-1506.
Nixon TRW, Alexander P, Richards A, et al. Homozygous Type IX collagen variants (COL9A1, COL9A2, and COL9A3) causing recessive Stickler syndrome-Expanding the phenotype. Am J Med Genet A. 2019;179(8):1498-1506.
Nixon, T. R. W., Alexander, P., Richards, A., McNinch, A., Bearcroft, P. W. P., Cobben, J., & Snead, M. P. (2019). Homozygous Type IX collagen variants (COL9A1, COL9A2, and COL9A3) causing recessive Stickler syndrome-Expanding the phenotype. American Journal of Medical Genetics. Part A, 179(8), 1498-1506. https://doi.org/10.1002/ajmg.a.61191
Nixon TRW, et al. Homozygous Type IX Collagen Variants (COL9A1, COL9A2, and COL9A3) Causing Recessive Stickler syndrome-Expanding the Phenotype. Am J Med Genet A. 2019;179(8):1498-1506. PubMed PMID: 31090205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homozygous Type IX collagen variants (COL9A1, COL9A2, and COL9A3) causing recessive Stickler syndrome-Expanding the phenotype. AU - Nixon,Thomas R W, AU - Alexander,Philip, AU - Richards,Allan, AU - McNinch,Annie, AU - Bearcroft,Philip W P, AU - Cobben,Jan, AU - Snead,Martin P, Y1 - 2019/05/14/ PY - 2018/11/29/received PY - 2019/02/13/revised PY - 2019/04/15/accepted PY - 2019/5/16/pubmed PY - 2020/8/4/medline PY - 2019/5/16/entrez KW - Stickler KW - retina KW - retinal detachment KW - sensorineural hearing loss KW - vitreoretinal SP - 1498 EP - 1506 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 179 IS - 8 N2 - Stickler syndrome (SS) is characterized by ophthalmic, articular, orofacial, and auditory manifestations. SS is usually autosomal dominantly inherited with variants in COL2A1 or COL11A1. Recessive forms are rare but have been described with homozygous variants in COL9A1, COL9A2, and COL9A3 and compound heterozygous COL11A1 variants. This article expands phenotypic descriptions in recessive SS due to variants in genes encoding Type IX collagen. Clinical features were assessed in four families. Genomic DNA samples derived from venous blood were collected from family members. Six affected patients were identified from four pedigrees with variants in COL9A1 (one family, one patient), COL9A2 (two families, three patients), and COL9A3 (one family, two patients). Three variants were novel. All patients were highly myopic with congenital megalophthalmos and abnormal, hypoplastic vitreous gel, and all had sensorineural hearing loss. One patient had severe arthropathy. Congenital megalophthalmos and myopia are common to dominant and recessive forms of SS. Sensorineural hearing loss is more common and severe in recessive SS. We suggest that COL9A1, COL9A2, and COL9A3 be added to genetic screening panels for patients with congenital hearing loss. Although recessive SS is rare, early diagnosis would have a high impact for children with potentially dual sensory impairment, as well as identifying risk to future children. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/31090205/Homozygous_Type_IX_collagen_variants__COL9A1_COL9A2_and_COL9A3__causing_recessive_Stickler_syndrome_Expanding_the_phenotype_ L2 - https://doi.org/10.1002/ajmg.a.61191 DB - PRIME DP - Unbound Medicine ER -