Type 1 Stickler syndrome: a histological and ultrastructural study of an untreated globe

Abstract

Aims To present a histological and ultrastructural study of an untreated globe in a patient with genetically confirmed type 1 Stickler syndrome. Methods Histological and electron microscopic examinations were performed on the enucleated globe from the proband of a pedigree with type 1 Stickler syndrome. Linkage analysis was carried out using polymorphic markers flanking the COL2A1 gene and the mutation was identified by direct sequencing. Results The significant retinal abnormality was incarceration of vitreous collagen within glial strands on the inner surface of an atrophic and gliotic detached retina. The incarcerated collagenous layers contained glial cells and extended from the retina to form strands, some of which contributed to a retrolental membrane. Mutation screening detected a C to T mutation in exon 47 that inserted a premature termination codon into the reading frame of the mRNA. Sequence analysis of three of the four affected children confirmed that they were also heterozygous for the base change. The youngest child's DNA was not analysed. Conclusions The study represents the first evidence of abnormal interactions between pathological vitreous collagen and the inner retina in a patient with type 1 Stickler syndrome with a confirmed mutation in the COL2A1 gene.

Characteristics of a Three-Generation Family with Stickler Syndrome Type I Carrying Two Different COL2A1 Mutations

“…In the milder forms, as typically seen in Stickler Syndrome type I, joints are more affected than bones [ 4 , 5 ]. In these cases, the mutant type II collagen seems to be able to form fibrils, albeit abnormal, which leads to progressive degeneration [ 23 ]. In more severe forms, leading to skeletal dysplasia, the mutant type II collagen is unable to assemble into fibrils, resulting in endoplasmic reticulum-mediated chondrocyte apoptosis and extracellular matrix loss [ 24 , 25 ].…”

Netzhautablösung im Kindesalter: Differenzialdiagnose und aktuelle Therapieoptionen

“…Die Mehrheit der betroffenen Patienten weist eine Mutation des COL2A1-Gens auf und bildet membrançse Glaskçrperstruk-turen (Typ1) aus, während beim Phänotyp 2 Mutationen des COIL11A1-Gens auftreten. Dies ist mit membranartigen Glaskçr-perverdichtungen assoziiert, weiterhin kçnnen Mutationen der Gene COL11A2 und COL9A1 auftreten[64,104,105]. Die häufigs-te okuläre Komplikation ist eine Netzhautablçsung, es wird eine Inzidenz von 48 bis 73% angegeben [3, 104].…”