Table 1.
Demographic Features of 15 Japanese Patients from 12 Families with GUCY2D-Associated Retinal Disorder (GUCY2D-RD)
| Refraction | LogMAR VA | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Family No. | Patient No. | Inheritance | Sex | Age (at Latest Examination) | Onset | Chief Complaint | Other ocular symptoms | RE | LE | RE | LE | Phenotype Subgroup | Inheritance Suggested by Molecular genetic diagnosis | Genotype |
| 1 (MU01) | 1-II:2 (Patient 1) | Sporadic | F | 1 | 0 | Reduced visual acuity/poor visual acuity | Nystagmus | NA | NA | NA | NA | LCA | AR | c.167_168delTG, p.Val56GlyfsTer262; c.738G>C, p.Met246Ile |
| 2 (TMC01) | 2-II:2 (Patient 2) | Sporadic | M | 12 | 3 | Reduced visual acuity/ poor visual acuity | Night blindness | −1 | −1 | 0.22 | 0.22 | CORD (moderate) | AR | c.238_252del, p.Ala80_Leu84del; c.2620G>A, p.Glu874Lys |
| 3 (NU01) | 3-II:7 (Patient 3) | Sporadic | M | 73 | NA | Night blindness | NA | +1.5 | +3.5 | 1 | 1.52 | CORD (severe) | AD | c.2281C>T, p.Arg761Trp |
| 4 (KDU01) | 4-III:1 (Patient 4) | AD | M | 30 | 23 | Reduced visual acuity/ poor visual acuity | NA | −2.5 | 2.5 | 0.82 | 0.82 | CORD (moderate) | AD | c.2512C>T, p.Arg838Cys |
| 4 (KDU01) | 4-II:2 (Patient 5) | AD | F | 61 | 21 | Reduced visual acuity/ poor visual acuity | Photophobia | −1.5 | −1.5 | 1.05 | 1.05 | CORD (moderate) | AD | c.2512C>T, p.Arg838Cys |
| 5 (GU01) | 5-III:5 (Patient 6) | AD | F | 31 | 18 | Reduced visual acuity/ poor visual acuity | Photophobia | −7 | −7 | 0 | 0.1 | CORD (mild) | AD | c.2513G>A, p.Arg838His |
| 6 (TMC02) | 6-III:1 (Patient 7) | AD | M | 38 | 7 | Reduced visual acuity/ poor visual acuity | Photophobia | −5 | −5 | 1.52 | 1.52 | CORD (severe) | AD | c.2513G>A, p.Arg838His |
| 7 (JU01) | 7-II:5 (Patient 8) | AD | F | 36 | 35 | Reduced visual acuity/ poor visual acuity | NA | −6 | −6.5 | 0.22 | 0.52 | CORD (mild) | AD | c.2513G>A, p.Arg838His |
| 7 (JU01) | 7-II:3 (Patient 9) | AD | F | 43 | 30 | Reduced visual acuity/ poor visual acuity | NA | −6 | −6.5 | 0.7 | 0.7 | CORD (moderate) | AD | c.2513G>A, p.Arg838His |
| 7 (JU01) | 7-I:2 (Patient 10) | AD | M | 68 | NA | NA | NA | +1 | −2 | 0.82 | 1 | CORD (NA) | AD | c.2513G>A, p.Arg838His |
| 8 (JU02) | 8-II:2 (Patient 11) | Sporadic | M | 23 | 23 | Photophobia | Color vision abnormality | −11.5 | −11.5 | 0.15 | 0.15 | CORD (mild) | AD (de novo) | c.2513G>A, p.Arg838His |
| 9 (KDU02) | 9-III:3 (Patient 12) | Sporadic | M | 64 | 41 | Reduced visual acuity/ poor visual acuity | NA | NA | NA | NA | NA | CORD (NA) | AD | c.2521G>A, p.Glu841Lys |
| 10 (TMC03) | 10-II:2 (Patient 13) | Sporadic | M | 10 | 0 | Reduced visual acuity/ poor visual acuity | Photophobia | +1.5 | +1.5 | 1 | 1 | CORD (moderate) | AD (de novo) | c.2704G>T, p.Val902Leu |
| 11 (NU02) | 11-II:2 (Patient 14) | Sporadic | M | 43 | NA | Reduced visual acuity/ poor visual acuity | Central visual field loss | −10 | −12 | 0.8 | 0.6 | CORD (moderate) | AD | c.2747T>C, p.Ile916Thr |
| 12 (MU02) | 12-II:5 (Patient 15) | Sporadic | F | 71 | 55 | Reduced visual acuity/ poor visual acuity | Photophobia | 0 | 0 | 0.52 | 0.52 | MD | AD | c.2747T>C, p.Ile916Thr |
AD, autosomal dominant; AR, autosomal recessive; CORD, cone rod dystrophy; F, female; LCA, Leber congenital amaurosis; LE, left eye; M, male; NA, not available; RE, right eye; LogMAR VA, best corrected logarithm of the minimum angle of resolution visual acuity; MD, macular dystrophy.
Autosomal dominant family history (at least having two affected subjects in two consecutive generations) was clearly reported in four families. Age described in the column was defined as the age when the latest examination was performed. The age of onset was defined as either the age at which visual loss was first noted by the patient or, in the “asymptomatic” patients, when an abnormal retinal finding was first detected. Patients 10 and 14 had cataract.
The phenotype subgroup was defined based on clinical findings, such as disease onset, symptoms, natural course, affected part on retinal imaging, the pattern of retinal dysfunction, and the history and phenotype of affected family members, partially according to the previous report: LCA (including early-onset RP), a severe retinal dystrophy with early-onset (<10 years) and complete loss of retinal function; RP (including rod-cone dystrophy), a progressive retinal dystrophy initially often affecting the peripheral retina with generalized rod dysfunction; CORD, a progressive retinal dystrophy initially often affecting the macula with generalized cone dysfunction; MD, a progressive retinal dystrophy presenting macular atrophy with confined macular dysfunction despite no abnormal generalized retinal function; and SNB, a stationary night blindness presenting congenital or early-onset night blindness often affecting generalized rod function despite essentially normal visual acuity and no atrophy.
There were two severe CORD subjects with poor VA and severe retinal dysfunction (patients 3, 7), six moderate CORD subjects with intermediate severity of VA or retinal function (patients 2, 4, 5, 9, 13, 14), and three mild CORD subjects with relatively favorable VA and relatively preserved generalized rod function (patients 6, 8, 11). Two subjects with CORD were unavailable for severity assessment due to unavailable VA or electrophysiological data.
Sequence variant nomenclature was performed according to the guidelines of the Human Genome Variation Society.