A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction.
OBJECTIVE
To describe the clinical findings of a patient with an early onset retinal dystrophy and a novel mutation in OTX2, and to compare these findings with previously reported cases.


METHODS
Using direct sequencing, we screened 142 patients, who had either Leber congenital amaurosis (LCA) or early onset retinal dystrophy (EORD), for mutations in OTX2. All patients received a detailed ophthalmic examination including electroretinography and retinal imaging.


RESULTS
Only one mutation in OTX2 was identified. A novel heterozygous p.S138X stop mutation was identified in a seven-year-old male who had an infantile onset retinal dystrophy. The mutation was not present in either parent or in 181 blood donor samples. There was a history of failure to thrive in infancy, poor feeding, and growth hormone deficiency. Poor vision and nyctalopia was present from the first year. Funduscopy revealed a hyperpigmented peripapillary ring with a fine granular pigmentation of the RPE throughout the fundus. The scotopic bright flash ERG a-wave was subnormal and the waveform electronegative, in keeping with dysfunction both at the level of the photoreceptor and post-phototransduction. Visual function has been stable to date.


CONCLUSIONS
Mutations in OTX2 have been reported in association with major developmental malformations of the eye, with retinal dystrophies such as LCA, and with pituitary dysfunction and seizure activity in some cases. This case adds further support for a role of OTX2 both in retinal development and pituitary function, and highlights a novel retinal dystrophy phenotype seen in association with mutations in OTX2.
Henderson
Robert H
RH
Moorfields Eye Hospital, London, United Kingdom.
Williamson
Kathleen A
KA
Kennedy
Joanna S
JS
Webster
Andrew R
AR
Holder
Graham E
GE
Robson
Anthony G
AG
FitzPatrick
David R
DR
van Heyningen
Veronica
V
Moore
Anthony T
AT
D017668:Age of Onset; D001483:Base Sequence; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005654:Fundus Oculi; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D051857:Otx Transcription Factors / Q000235:genetics*; D010641:Phenotype; D010900:Pituitary Diseases / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D012164:Retinal Diseases / Q000150:complications / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D012606:Scotland / Q000453:epidemiology
D018389:Codon, Nonsense; C497659:OTX2 protein, human; D051857:Otx Transcription Factors