Analysis of gene mutations in lecithin cholesterol acyltransferase deficiency and fish eye disease of Japanese cases

Abstract

Purpose : Familial lecithin cholesterol acyltransferase (LCAT) deficiency and fish eye disease (FED) are autosomal recessive disorders caused by mutations in LCAT gene, that is located in 16q22 chromosome. We revealed genetic mutations in LCAT and apolipoprotein-A1 (Apo-A1) in LCAT deficiency and FED by exome sequencing analysis.

Methods : Four cases of bilateral diffuse corneal opacity with low serum LCAT activity, low Apo-A1 level and low HDL cholesterol level were selected. All four cases were adult women with onset of corneal opacity in adolescent or adulthood without a history of cardiovascular events. Three cases were diagnosed as FED from normal renal function and hematological data. One case was diagnosed as LCAT deficiency from renal dysfunction, hemolytic anemia and low LDL cholesterol level. This case had a sibling, who had no corneal opacity. We analyzed genetic mutations of Apo-A1 and LCAT genes using exome sequencing analysis with confirmation by dideoxy sequencing.

Results : No mutation was found in Apo-A1 in all four cases. LCAT gene in three FED cases showed homozygous mutations of the exon 4 region; c.440 c > t, p.T147I in 2 cases and c.428 g > a, p.G143E in one case. The LCAT deficiency patient had homozygous mutation of exon 6, c.1102 g>a, p.G368S, and her sibling had heterozygous mutation of this site.

Conclusions : The presented patients had homozygous one point mutation of LCAT gene. In this study point mutations in the exon 4 is associated with FED and that in the exon 6 with LCAT deficiency. c.428 g > a, p.G143E in FED has not been reported. Exome sequencing analysis is a useful tool to investigate FED and LCAT deficiency.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.