A molecular-genetic study of Congenital Nystagmus
University of Southampton, School of Medicine,
Nystagmus is a disorder of eye movement characterised by irregular, uncontrolled and
repetitive eye movements. It can occur in a broad spectrum of clinical situations and
diseases or it may occur in isolation and an inherited disorder. Surprisingly little is
known about the underlying mechanisms of ocular-motor control. Similarly, the
pathophysiological mechanisms underpinning nystagmus is also poorly understood. By
studying pedigrees in whom nystagmus seems to be inherited as an isolated trait
(Congenital Idiopathic Nystagmus), it may be possible to identify some of the genetic
causes of this disorder and subsequently understand the pathophysiology.
This thesis describes a molecular genetic study of congenital nystagmus. A clinical
phenotyping study is followed by linkage analysis and positional cloning. A novel
nystagmus gene is investigated in a large cohort of Congenital Idiopathic Nystagmus
(CIN) patients and X-inactivation studies are performed. Subsequently, cell culture and
RT-PCR work is performed to study expression of this gene. Additionally a pedigree with
an atypical congenital nystagmus disorder is investigated and a new mutation within a
known cerebellar disease gene is identified.
This work contributed to the identification of the first gene for Congenital Idiopathic
Nystagmus (CIN). The first detailed temporal expression study of the FRMD7 nystagmus
gene was also performed in this study which has directed further studies into the
pathogenesis of CIN. Identification of a new mutation in the CACNA1A gene in a
pedigree with nystagmus and subtle cerebellar signs has lead to the consideration of
this gene in patients who present to hospital with isolated atypical nystagmus.
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