Association of familial macular degeneration with specific genetic markers: a case report

Age-related macular degeneration (AMD) is a serious visual disorder of the central
retina and it is prevalent in developed countries 1], 2]. In Asian patients, exudative (wet) AMD occurs more frequently than geographic atrophy
(dry) AMD seen in European patients with late AMD 3], 4]. Choroidal vasculopathy around the macula triggers abnormal neovascularization, leading
to serious hemorrhaging and exudation 5]. For most European patients, without such hemorrhages, retinal thinning is accompanied
by atrophy of the retinal pigment epithelium 5].

Irrespective of similarities in phenotypic defects among AMD types, the mechanisms
underlying the development of AMD are not well understood. However, from the familial
incidence of AMD, genetic background has been suspected and, accordingly, genes associated
with AMD have been identified for both the dry and wet types of AMD 6]–8]. Recent genetic association studies have been successful in identifying several AMD
risk-associated single nucleotide polymorphism (SNP) variants, and the SNP variants
are specific to AMD type, reflecting different genetic backgrounds among races. Through
genome-wide association studies (GWASs) on large populations of patients with AMD
that included independent groups, several SNP susceptibility variants were identified
in genes encoding complement factor H (CFH), high-temperature requirement factor A1 (HTRA1) and age-related maculopathy susceptibility 2 (ARMS2), as well as in the regions for TNFSF10A-LOC389641 and REST-C4orf14-POLR2B-IGFBP7
for dry-type 9] and for wet-type AMD 10], 11].

Diagnosis of AMD is certified for patients over 50 years of age, but there is also
a group of patients with AMD with early onset 1], 2]. For such patients, hereditary SNP variation in loci associated with AMD is assumed.
We report here an Asian case of familial AMD with early onset bearing both of the
known high-risk SNP variants (rs10490924 and rs11200638 in ARMS2 and HTRA1, respectively) 10], 11] in patients with AMD, suggesting a genetic association between the two SNPs in AMD
onset.