GPR143

Nystagmus 6, Congenital, X-linked

Clinical Characteristics
Ocular Features: 

In several Chinese families, nystagmus was limited to males with onset in one case in the first 6 months.  Foveal dysplasia was present along with mottled fundus pigmentation.  Carrier females did not have nystagmus or changes in fundus pigmentation (except for one with mottling). Vision is in the range of 20/50-20/60.

Systemic Features: 

Skin and hair pigmentation was normal. No systemic disease was identified.

Genetics

Mutations in GPR143 (Xp22.2) have been identified in this form of nystagmus. The family pedigrees are consistent with X-linked recessive inheritance.

Two additional X-linked isolated nystagmus conditions are contained in this database: nystagmus 1 (310700), the result of mutations in FRMD7, and nystagmus 5 (300589) of unknown gene causation.

Several autosomal dominant forms have been linked to chromosomal regions 6p12 (NYS2; 164100), 7p11 (NYS3, 608345), 13q (NYS4, 193003), 1q31.3-q32.1, and NYS7 (614826).  Autosomal recessive inheritance has been proposed for several pedigrees but adequate documentation is lacking (see 257400).

Ocular albinism (OA1) (300500) can also result from mutations in GPR143.  However, there was no evidence of ocular or systemic hypopigmentation in the Chinese families.

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Aprataxin gene mutations in Tunisian families

Amouri R, Moreira MC, Zouari M, El Euch G, Barhoumi C, Kefi M, Belal S, Koenig M, Hentati F. Aprataxin gene mutations in Tunisian families. Neurology. 2004 Sep 14;63(5):928-9.

PubMed ID: 
15365154

Albinism, Ocular Type 1

Clinical Characteristics
Ocular Features: 

Signs in ocular albinism include hypopigmentation of the fundus with clearly visible choroidal vessels, foveal hypoplasia, and hypopigmentation of the iris. Strabismus, nystagmus, photophobia, absent stereoacuity and high refractive errors including hypermetropia are other common features.  Vision may be near normal but usually worse, in the range of 20/100 to 20/300.  In at least some patients with ocular albinism, concentric macular rings have been identified using infrared reflectance images.

In ocular albinism there is a nearly complete crossing of nerve fibers in the optic chiasm as well as a decreased number of photoreceptors.  MRI imaging of the optic chiasm in humans with albinism reveals it to be smaller with a wider angle between optic tracts, reflecting the atypical crossing of nerve fibers.

This is an X-linked recessive disorder and affects mainly men. In 80% of female carriers a mosaic of pigmentary changes can be observed in the fundus, especially in the periphery as a result of lyonization.  A few female heterozygotes have ocular changes of albinism including nystagmus and reduced visual acuity, likely as a result of unequal X-chromosome inactivation.  Perhaps three-quarters of carrier females have transillumination defects in the iris.

Hearing loss is often associated with pigmentation disorders and one large family with X-linked ocular albinism has been reported with a late onset sensorineural deafness (300650).  The ocular findings are typical but deafness is not significant until late midlife.

Systemic Features: 

In ocular albinism, pigmentation is normal except in the eye.  Hearing loss has been reported in a single family but this may be a unique disorder since the genotype was not determined.

Genetics

Ocular albinism (OA1) is a recessive X-linked disorder, caused by mutations in the GPR143 gene, located at Xp22.3.  The protein product, a G protein-coupled receptor, is localized on the membrane of melanosomes in pigmented cells in the eye.  The same gene is mutated in congenital nystagmus 6 (300814).  Ocular albinism with late onset sensorineural deafness (300650) results from mutations in the Xp22.3 region as well and may or may not be the same condition.

It has been reported that mutations in GNA13 (17q24.1), activated by OA1, can also result in the ocular albinism phenotype.

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment
Treatment Options: 

Treatment for the ocular symptoms is targeted toward specific problems. Refractive errors are treated with corrective glasses with tinted lenses recommended for the photophobia. Low vision aids and special education may be required.

References
Article Title: 
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