GJA8

Cataracts, Congenital Zonular Pulverulent 1

Clinical Characteristics

Ocular Features:

Bilateral lens opacities may be both nuclear and zonular. The embryonic and fetal nuclei are usually involved and diffuse cortical opacities may also be seen in some patients. The involved area is therefore larger than the somewhat similar Coppock-like cataract (604307) which is limited to the embryonic nucleus. The lens opacities may be seen at birth or in early childhood and usually progress. There is considerable clinical variation in the degree and distribution of the usual dust-like opacities which may also be lamellar in distribution with a clear peripheral cortex and minimal nuclear involvement. Microcornea has also been reported. In mild cases the lens opacities are primarily clustered along the Y sutures resembling congenital zonular cataracts with sutural opacities (600881).

Three unrelated patients with mutations in GJA8 and total sclerocornea have been reported. Two of these patients in addition had small abnormal lenses while the third had cataracts and micropthalmia. Two of the three also develped glaucoma by one year of age.

The nature and morphology of the lens opacities in an adult have been studied by light and scanning electron microscopy. They are located in the embryonic and fetal nuclei and appear "puffy" with lens fiber irregulaties and entanglement in adjacent areas.

Systemic Features:

None.

Genetics

Congenital zonular pulverulent cataracts are inherited in an autosomal dominant pattern resulting from missense mutations in the GJA8 gene (1q21.1) that codes for connexin 50. These belong to a category of lens opacitites now designated "Cataract 1, Multiple Types" in OMIM (116200). They have been detected in multiple populations and ethnic groups around the world.

Mutations in CZP3 at 13q11-13 coding connexin 46 (601885) result in a similar phenotype (Cataracts, Congenital Zonular Pulverulent 3) suggesting that genetic heterogeneity is present.

This was the first disease locus to be linked on a human autosome, in this case to the Duffy blood group locus on chromosome 1.

Pedigree:

Autosomal dominant

Treatment

Treatment Options:

Cataract surgery is indicated for visually significant lens opacities which may be required late in the first or early in the second decade of life.

References

Article Title:

New mutations in GJA8 expand the phenotype to include total sclerocornea

Ma AS, Grigg JR, Prokudin I, Flaherty M, Bennetts B, Jamieson RV. New mutations in GJA8 expand the phenotype to include total sclerocornea. Clin Genet. 2017 Apr 29. doi: 10.1111/cge.13045. [Epub ahead of print].

PubMed ID:

28455998

A novel connexin 50 (GJA8) mutation in a Chinese family with a dominant congenital pulverulent nuclear cataract

Yan M, Xiong C, Ye SQ, Chen Y, Ke M, Zheng F, Zhou X. A novel connexin 50 (GJA8) mutation in a Chinese family with a dominant congenital pulverulent nuclear cataract. Mol Vis. 2008 Mar 4;14:418-24.

PubMed ID:

18334966

Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3)

Rees MI, Watts P, Fenton I, Clarke A, Snell RG, Owen MJ, Gray J. Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3). Hum Genet. 2000 Feb;106(2):206-9.

PubMed ID:

10746562

A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q

Shiels A, Mackay D, Ionides A, Berry V, Moore A, Bhattacharya S. A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q. Am J Hum Genet. 1998 Mar;62(3):526-32.

PubMed ID:

9497259

Probable assignment of the Duffy blood group locus to chromosome 1 in man

Donahue RP, Bias WB, Renwick JH, McKusick VA. Probable assignment of the Duffy blood group locus to chromosome 1 in man. Proc Natl Acad Sci U S A. 1968 Nov;61(3):949-55.

PubMed ID:

5246559

PROBABLE LINKAGE BETWEEN A CONGENITAL CATARACT LOCUS AND THE DUFFY BLOOD GROUP LOCUS

RENWICK JH, LAWLER SD. PROBABLE LINKAGE BETWEEN A CONGENITAL CATARACT LOCUS AND THE DUFFY BLOOD GROUP LOCUS. Ann Hum Genet. 1963 Aug;27:67-84.

PubMed ID:

14059288

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