Corneal dystrophies in Japan

Abstract

Recent advances in molecular genetics have increased our understanding of the role of genes. Four autosomal dominant corneal dystrophies (CDs); granular CD (GCD), Avellino CD (ACD), lattice CD (LCD), and ReisBücklers CD (RBCD) were mapped to the long arm of chromosome 5 (5q31). These four diseases were shown, in a Caucasian series, to result from different missense mutations in the TGFBI (BIGH3, keratoepithelin) gene. The same mutations were also detected in Japanese patients, from a different ethnic background. Gelatinous drop-like corneal dystrophy (GDLD), on the other hand, which was found in Japanese patients in 1914, is a rare autosomal recessive disorder characterized by corneal amyloidosis. Parents of the patients had a markedly higher frequency of consanguineous marriages than the general population. The gene responsible for GDLD, the membrane component, chromosome 1, surface marker 1 (M1S1) gene was mapped to the short arm of chromosome 1(1p). Four deleterious mutations in this gene were detected in Japanese patients. We review here additional studies on mutations of the TGFBI and M1S1 genes found in Japanese patients. In the TGFBI gene, nine different mutations were detected in Japanese patients with GCD, ACD, LCD, or RBCD. The codons R124 and R555 of the TGFBI gene were hotspots in Japanese patients, of whom many were ACD patients with the R124H mutation. New mutations responsible for LCD were detected in the TGFBI gene of patients with LCD, in addition to the P501T mutation in LCD type IIIA found earlier. These studies showed a clear genotype/phenotype correlation associated with the TGFBI gene. In the M1S1 gene, the Q118X mutation was the most common alteration, and a founder mutation in Japanese GDLD patients, as previously reported. Ninety-two percent of the mutated alleles were the Q118X.

Surgical outcome after phototherapeutic keratectomy in patients with TGFBI-linked corneal dystrophies in relation to molecular genetic findings

“…Based on the knowledge of the molecular genetics of the corneal dystrophies their diagnosis should now be determined by the molecular genetic results [1][2][3][4][5][6][7][8][12][13][14][15][16][17][18][19][20][21][22][23][24].…”

“…Most patients have mutations at mutational hot spots corresponding to arginine 124 and arginine 555 of the keratoepithelin protein. Such mutations are the arginine 124 to cysteine mutation (Arg124Cys) leading to lattice corneal dystrophy I (CDLI), the arginine to histidine mutation (Arg124His) leading to Avellino dystrophy (CDA), the arginine to leucine mutation (Arg124Leu) leading to Reiss-Bucklers corneal dystrophy (CDBI), the arginine to tryptophane mutation (Arg555Trp) leading to granular corneal dystrophy I (CDGGI) and the arginine to glutamine mutation (Arg555Gln) leading to either CDBI or Thiel-Behnke corneal dystrophy (CDBII) [11][12][13][14][15][16][17][18]. In some patients with CDBII, linkage analysis revealed the underlying molecular genetic defect at chromosome 10q24, which involves an as yet-unknown gene.…”

Gelatinous drop-like corneal dystrophy in a child with developmental delay: clinicopathological features and exclusion of the M1S1 gene

“…4,5 It presents in the first decade of life with bilateral, axial, elevated, mulberry-like or gelatinous lesions, due to amyloid deposition in the superficial cornea. With time, the cornea vascularises and the deposits spread laterally and deeply within the stroma, leading to a progressive loss in vision.…”

Mutation Analysis of the TGFBI Gene in Vietnamese with Granular and Avellino Corneal Dystrophy

“…6 Reports from researchers of various nationalities (Japanese, Canadian, American, French, Italian, German, Austrian, Korean, Norwegian 6-11 ) also described R555W and R124H mutations as the primary cause of GCD and ACD, respectively. Regarding the relative ratio between these two dystrophies, in Asians such as Japanese and Koreans the R124H mutation-associated ACD phenotype was reported as the most common (Ͼ90%), 11,12 whereas in Caucasians the GCD phenotype caused by the R555W mutation was most common.…”