Bilateral congenital or childhood onset cataracts

Gene: SIPA1L3

PMID: 25804400 - two sisters with dense white cataracts reported to be homozygous for a nonsense variant in this gene. This was heterozygous in the unaffected parents. PMID: 26231217 - One patient who had lens and ocular anterior segment abnormalities reported with a de novo balanced translocation 46,XY,t(2;19)(q37.3;q13.1). The breakpoint transected SIPA1L3 at 19q13.1, and they report reduced SIPA1L3 expression in patient lymphoblasts. A second patient with cataracts was heterozygous for a missense variant in SIPA1L3, c.442G>T, p.Asp148Tyr. In vitro studies of the variant in an epithelial cell line showed abnormal clustering of actin stress fibres and decreased formation of adherens junctions. Parental DNA samples were unavailable for study to confirm segregation. PMID: 27993984 In Xenopus, loss of Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes and lenses including lens fiber cell maturation defects. PMID: 28951961 - further evidence provided by a study reporting a spontaneous mutation was identified in a mouse line that influenced lens formation and resulted in juvenile cataracts in mice homozygous for the recessive allele. Haplotype analysis revealed a 197.5 kb segment unique to cataract-affected mice that included a single known transcript consisting of the first 14 exons of Sipa1l3, predicted to cause a truncated protein. Affected mice were homozygous for the deletion and normal mice were either heterozygous or homozygous for the wild-type allele.

Created: 30 Oct 2017, 2:29 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
?Cataract 45

Publications

• 25804400
• 26231217
• 27993984