title: Progressive retinal degeneration in a girl with Knobloch syndrome who presented with signs of ocular albinism.
abstract: We report for the first time electroretinographic (ERG) evidence of progressive retinal abnormalities in a girl who presented in infancy with ocular features of albinism and gradually developed choroidal sclerosis and patchy retinal atrophy leading to a diagnosis of Knobloch syndrome (KS, OMIM 267750, COL18A1).
  
  
  
  At age 2 months, nystagmus and esotropia prompted ophthalmic evaluation. The appearance of choroidal sclerosis and atrophic retinal patches led to further evaluation at age 8 years. Genetics consultation was obtained in infancy and again at age 8 years as retinal findings evolved. Full field ERG responses in both scotopic and photopic conditions were recorded at both ages and compared to those in healthy control subjects.
  
  
  
  At age 2 months ERG response parameters were within normal limits for age and tyrosinase (TYR) gene sequencing revealed one novel mutation, p.S466F, and the temperature-sensitive polymorphism, p.R402Q, suggesting the diagnosis of oculocutaneous albinism type 1 (OCA1). At age 8 years, there was significant attenuation of both scotopic and photopic ERG responses. Genetic re-analysis led to the identification of a homozygous mutation, c.3213dupC, in the COL18A1 gene, thus confirming the diagnosis of Knobloch syndrome.
  
  
  
  Our patient with Knobloch syndrome developed abnormal ERG responses similar to those found in col18a1 knockout mice. Thus, we have documented progressive attenuation of the scotopic and photopic responses in KS.
authors.affiliation: Department of Ophthalmology, Soroka Medical Center and Clalit Health Services, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel.
authors.forename: Libe
authors.initials: L
authors.lastname: Gradstein
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave., Boston, MA, 02115-5737, USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Hansen
authors.affiliation: Division of Genetics and Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.|Editas Medicine, 11 Hurley St., Cambridge, 02141, MA, USA.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Cox
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave., Boston, MA, 02115-5737, USA.|Department of Ophthalmology, Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Altschwager
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave., Boston, MA, 02115-5737, USA. anne.fulton@childrens.harvard.edu.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Fulton
mesh_terms: D016117:Albinism, Ocular / Q000175:diagnosis*; D002648:Child; D018450:Disease Progression; D004596:Electroretinography; D004677:Encephalocele / Q000175:diagnosis*; D004948:Esotropia / Q000175:diagnosis; D005260:Female; D006801:Humans; D009759:Nystagmus, Pathologic / Q000175:diagnosis; D012160:Retina / Q000502:physiology; D012162:Retinal Degeneration / Q000175:diagnosis*; D012163:Retinal Detachment / Q000151:congenital* / Q000175:diagnosis
keywords: Albinism; Electroretinogram (ERG); Knobloch syndrome; Photoreceptor; Retinal degeneration; a-Wave; b-Wave