Two Chinese families with pulverulent congenital cataracts and ∆ G 91 CRYBA 1 mutations

Congenital or juvenile cataract is a critical diagnosis in pediatric ophthalmology [1]. Its early recognition and surgical intervention are essential to avoid irreversible visual loss, especially in the case of complete cataract [1,2]. If left untreated, normal retinal development will be impaired due to lack of sharp focus of light and sensory deprivation [2]. Congenital cataracts have an overall prevalence of 1 to about 6 per 10,000 live births [2], and comprise a group of clinically and genetically heterogeneous conditions. The patients are generally classified according to the type and location of the observed opacities including cataracts of anterior polar, posterior polar, nuclear, lamellar, pulverulent, aceuliform, cerulean, total, cortical, polymorphic, or sutural types [3]. Approximately one-third of patients with isolated congenital cataracts have a familial form of the disease preferentially with autosomal dominant inheritance (autosomal dominant congenital cataract [ADCC]) [4]. To date, 16 disease genes have been identified for ADCC and 10 additional loci are implicated from family studies [3,5,6]. Nine of the known disease genes are related to the normal formation and function of crystallins including αA-crystallin (CRYAA) [7,8], αB-crystallin (CRYAB) [9], βA1-crystallin (CRYBA1) [10,11], βA4-crystallin (CRYBA4) [6], βB1-crystallin (CRYBB1) [12], βB2-crystallin (CRYBB2) [13-15], γC-crystallin (CRYGC) [16,17], γD-crystallin (CRYGD) [18], and γS-crystallin (CRYGS) [5]. Crystallins are essential for maintenance of lens transparency and refraction [19]. The super family of crystallins comprises crystallins of α-, β-, or γ-crystallin types [20], among which the β-crystallins are most abundant in the lens. The CRYBA1 gene (also known as CRYBA3/A1 ) encodes the βcrystallin A3 isoform 1, a 215 aa protein with a molecular weight of 25 kDa. Following linkage in an affected family to chromosomal region 17q11-12 [10], CRYBA1 was first identified as a cause of cataract in a pedigree with autosomal dominant zonular cataract [11]. Consequently, CRYBA1 mutations were reported in several families [21-25]. In addition to three splice mutations at the donor splice site of intron 3 [11,21,22], ∆G91 mutations have been described in three affected families of different ethnic backgrounds [23-25]. ©2007 Molecular Vision