GJA3

Cataracts, Congenital Zonular Pulverulent 3

Clinical Characteristics

Ocular Features:

Bilateral dust-like lens opacities are diagnosed at a median age of 5 years but have been seen at 6 months of age. These affect the embryonal, fetal, and infantile nucleus and are often surrounded by snowflake- or needle-like opacities throughout the lens cortex. The dust-like particles may be multicolored and impart a haze to the lens. Evidence for progression is suggested by the fact that about half of such affected patients require cataract surgery as adults. No other ocular abnormalities are present.

There is considerable phenotypic heterogeneity.

Systemic Features:

No systemic abnormalities are associated.

Genetics

Heterozygous mutations in GJA3 (13q11) seem to be responsible for the opacities. For another somewhat similar form of autosomal dominant congenital cataract see Cataracts, Congenital Zonular Pulverulent 1 (116200).

Pedigree:

Autosomal dominant

Treatment

Treatment Options:

Visually significant cataracts may be removed.

References

Article Title:

A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance

Burdon KP, Wirth MG, Mackey DA, Russell-Eggitt IM, Craig JE, Elder JE, Dickinson JL, Sale MM. A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance. J Med Genet. 2004 Aug;41(8):e106. Erratum in: J Med Genet. 2005 Mar;42(3):288. J Med Genet. 2008 Apr;45(4):256.

PubMed ID:

15286166

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

Cataracts, Coppock-Like

Clinical Characteristics

Ocular Features:

Coppock-like cataracts consist of bilateral progressive opacities of the embryonic lens nucleus. They are characterized by a pulverulent opacification with a gray disc appearance associated with variable zonular opacities. Visual symptoms often begin during adolescence and some patients require cataract surgery by the 5^th decade of life.

Systemic Features:

There is no systemic disease associated with this type of cataract.

Genetics

CCL cataracts are embryonic in origin, developing during the time when gamma-crystallin genes are active. The gamma E-crystallin gene is a pseudogene and the mutation in its promoter reactivates its activity 10-fold. It is postulated that overexpression of the gamma-crystallin fragment is responsible for the nuclear opacification.

Mutations in at least 3 genes have been associated with this type of cataract. In some families the mutations are in the CRYGC gene (2q33-q35), and in others mutations in CRYBB2 (22q11.2-q12.2) seem to be responsible. It is of interest that one form of congenital cerulean cataract, CCA3 (608983), found in a single family, results in mutations in CRYGD also located at 22q11.2-q12.2. A five-generation Chinese family has been reported in which mutations in GJA3 (13q12.11) was associated with this type of lens opacity.

Other forms of autosomal dominantly inherited, congenital, progressive lens opacities include congenital cerulean (115660, 601547, 608983, 610202), Volkmann type (115665), lamellar (116800), and congenital posterior polar (116600) cataracts. Due to clinical heterogeneity, it is not always possible to classify specific families based on the appearance and natural history of the lens opacities alone.

Pedigree:

Autosomal dominant

Treatment

Treatment Options:

Cataract surgery may be indicated.

References

Article Title:

Genetic heterogeneity of the Coppock-like cataract: a mutation in CRYBB2 on chromosome 22q11.2

Gill D, Klose R, Munier FL, McFadden M, Priston M, Billingsley G, Ducrey N, Schorderet DF, H?(c)on E. Genetic heterogeneity of the Coppock-like cataract: a mutation in CRYBB2 on chromosome 22q11.2. Invest Ophthalmol Vis Sci. 2000 Jan;41(1):159-65.

PubMed ID:

10634616

Activation of the gamma E-crystallin pseudogene in the human hereditary Coppock-like cataract

Brakenhoff RH, Henskens HA, van Rossum MW, Lubsen NH, Schoenmakers JG. Activation of the gamma E-crystallin pseudogene in the human hereditary Coppock-like cataract. Hum Mol Genet. 1994 Feb;3(2):279-83.

PubMed ID:

8004095

A novel mutation in GJA3 associated with congenital Coppock-like cataract in a large Chinese family

Zhang L, Qu X, Su S, Guan L, Liu P. A novel mutation in GJA3 associated with congenital Coppock-like cataract in a large Chinese family. Mol Vis. 2012;18:2114-8.

PubMed ID:

22876138

Cataracts, Congenital, Autosomal Dominant

Clinical Characteristics

Ocular Features:

Most cataracts arise as part of the aging process. However, early onset lens opacities may be familial, often transmitted in an autosomal dominant pattern. These have a highly variable appearance and may be unilateral or bilateral. There can be considerable interocular asymmetry in morphology, density, location, and rate of progression. This is also true of intrafamilial characteristics. Age of onset is variable.

Systemic Features:

There are no associated systemic abnormalities.

Genetics

At least 25 loci scattered among multiple chromosome have been identified to cause simple autosomal dominant cataracts (See 604219). It is not yet possible to make phenotypic - genotypic correlations due to the large variation in clinical characteristics.

Pedigree:

Autosomal dominant

Treatment

Treatment Options:

Lens extraction is indicated when the opacities become visually significant.

References

Article Title:

A Novel CRYBB2 Missense Mutation Causing Congenital Autosomal Dominant Cataract in an Italian Family

Faletra F, d'Adamo AP, Pensiero S, Athanasakis E, Catalano D, Bruno I, Gasparini P. A Novel CRYBB2 Missense Mutation Causing Congenital Autosomal Dominant Cataract in an Italian Family. Ophthalmic Genet. 2012 Jul 30. [Epub ahead of print].

PubMed ID:

22846113

Autosomal dominant cataract: intrafamilial phenotypic variability, interocular asymmetry, and variable progression in four Chilean families

Shafie SM, Barria von-Bischhoffshausen FR, Bateman JB. Autosomal dominant cataract: intrafamilial phenotypic variability, interocular asymmetry, and variable progression in four Chilean families. Am J Ophthalmol. 2006 Apr;141(4):750-2.

PubMed ID:

16564818

Clinical and genetic heterogeneity in autosomal dominant cataract

Ionides A, Francis P, Berry V, Mackay D, Bhattacharya S, Shiels A, Moore A. Clinical and genetic heterogeneity in autosomal dominant cataract. Br J Ophthalmol. 1999 Jul;83(7):802-8.

PubMed ID:

10381667

Autosomal dominant congenital cataract. Interocular phenotypic variability

Scott MH, Hejtmancik JF, Wozencraft LA, Reuter LM, Parks MM, Kaiser-Kupfer MI. Autosomal dominant congenital cataract. Interocular phenotypic variability. Ophthalmology. 1994 May;101(5):866-71.

PubMed ID:

8190472

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