Table 1 Clinical characteristics and genotype of the patients with USH2A-related disease without early-onset hearing loss (discovery cohort)

From: A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants

Subject; family ID

Age *; gender

VA (LogMAR)

Presenting symptom (age)

Hearing loss

USH2A sequencing results b

FAF

Comments

Ethnicity

  

RE

LE

 

Subjective

Audiology a

    

D1; gc4627

34; M

0.00

0.18

NA

No

NA

c.[2276G>T(;)13010C>T], p.[(Cys759Phe)(;)(Thr4337Met)]

NA

—

European

D2; gc16390

35; M

0.00

−0.10

Nyctalopia (23 y.o.)

No

Group 3

c.[2299delG(;)12295-3T>A], p.[(Glu767Serfs *21)];[?]

Ring BE

—

European

D3; gc15522

41; M

0.18

0.18

Nyctalopia (17 y.o.)

No

Group 1 A

c.[2276G>T(;)13316C>T], p.[(Cys759Phe)(;)(Thr4439Ile)]

Ring BE

—

European

D4; gc5134

42; F

2.20

0.48

Nyctalopia (20 y.o.)

No

Group 1A

c.[3724C>T(;)3724C>T], p.[(Pro1242Ser)(;)(Pro1242Ser)]

Atrophy BE

—

South Asian

D5; gc17134

42; F

0.24

0.10

Loss of peripheral vision (26 y.o.)

No

Group 1A

c.[2276G>T(;)2276G>T], p.[(Cys759Phe)(;)(Cys759Phe)]

Ring BE

CMO

European

D6; gc16520

42; F

0.30

0.18

Nyctalopia (27 y.o.)

Yes

NA

c.[2276G>T(;)12575G>A], p.[(Cys759Phe)(;)(Arg4192His)]

Ring BE

CMO

European

D7; gc17055

43; M

0.48

0.60

Nyctalopia (15 y.o.)

Yes

NA

c.[2276G>T(;)15031delT], p.[(Cys759Phe)(;)(Tyr5011fs)]

Ring BE

—

European

D8; gc16986

47; F

0.00

0.00

Nyctalopia (36 y.o.)

No

Group 1A

c.[2299delG(;)10073G>A] p.[(Glu767Serfs*21)(;)(Cys3358Tyr)]

Ring BE

—

European

D8a; gc16986

48; F

0.18

0.18

Nyctalopia (42 y.o.)

No

Group 2

 

Ring BE

—

European

D8b; gc16986

58; F

0.60

0.60

Nyctalopia (38 y.o.)

Yes

Group 1B

 

Ring BE

CMO, IOL LE

European

D9; gc16172

48; M

−0.10

0.00

Nyctalopia (30 y.o.)

No

Group 1B

c.[2332G>T(;)2332G>T], p.[(Asp778Tyr)];[(Asp778Tyr)]

Ring BE

—

African

D14a; gc5204

50; M

0.48

0.60

Nyctalopia (18 y.o.)

No

NA

c.[2276G>T(;)14426C>T], p.[(Cys759Phe)(;)(Thr4809Ile)]

Ring BE

CMO

European

D14; gc5204

55; F

0.22

0.40

Dark adaptation (32 y.o.)

Yes

Group 1B

 

Ring BE

CMO

European

D10; gc16891

51; F

0.72

0.68

Nyctalopia (23 y.o.)

No

Group 1A

c.[5776+1G>A(;)9056-2A>G], p.[?];[?]

Small ring BE

—

European

D11a; gc1985

50; M

0.20

0.22

Nyctalopia (13 y.o.)

No

Group 2

c.[2299delG(;)12295-3 T>A], p.[(Glu767Serfs*21)];[?]

Small ring BE

CMO, IOL BE

European

D11; gc1985

52; F

0.28

0.42

Nyctalopia (17 y.o.)

No

Group 2

 

Small ring BE

IOL BE

European

D12; gc15971

52; M

0.22

0.08

Dark adaptation (42 y.o.)

No

Group 1A

c.[7595-3C>G(;)8546G>T], p.[Pro2533Asnfs*5(;)(Gly2849Val)]

Ring BE

CMO

European

D13; gc860

54; M

0.18

0.18

Nyctalopia (14 y.o.)

Yes

Group 1B

c.[12093C>A];[12295-3T>A], p.[(Tyr4031*)];[?]

Small ring BE

IOL BE

European

D15; gc4654

55; M

0.18

0.18

Nyctalopia (32 y.o.)

Yes

NA

c.[10073G>A(;)11156G>A], p.[(Cys3358Tyr)(;)(Arg3719His)]

Ring BE

—

European

D16; gc16801

55; M

0.18

0.00

Nyctalopia (30 y.o.)

No

NA

c.[2633G>A(;)3902G>T], p.[(Arg878His)(;)(Gly1301Val)]

NA

—

South Asian

D17; gc16524

56; F

0.78

0.78

Nyctalopia (35 y.o.)

No

Group 1A

c.[2276G>T(;)10073G>A], p.[(Cys759Phe)(;)(Cys3358Tyr)]

Central hyperAF BE

IOL BE

European

D18; gc5399

58; M

0.36

0.20

Nyctalopia (12 y.o.)

No

Group 1A

c.[2276G>T(;)2299delG], p.[(Cys759Phe)(;)(Glu767Serfs*21)]

Small ring BE

CMO

European

D19; gc5396

63; F

1.30

0.60

Nyctalopia (15 y.o.)

Yes

Group 1B

c.[2276G>T(;)2299delG], p.[(Cys759Phe)(;)(Glu767Serfs*21)]

Atrophy RE; Central hyperAF LE

CMO

European

D20; gc1802

66; F

0.50

1.30

Nyctalopia (28 y.o.)

No

NA

c.[14219C>A(;)11048-?_11711+?dup], p.[(Ala4740Asp)];[?]

Central hyperAF BE

—

European

D21; gc2053

68; M

2.20

2.20

Nyctalopia (15 y.o.)

No

Group 1A

c.[2802T>G(;)12575G>A], p.[(Cys934Trp)(;)(Arg4192His)]

Atrophy BE

—

European

D22; gc4737

69; M

−0.10

0.20

Nyctalopia (29 y.o.)

Yes

NA

c.[2276G>T(;)13010C>T], p.[(Cys759Phe)(;)(Thr4337Met)]

Small ring BE

IOL BE

European

D23; gc945

77; F

2.20

0.48

Nyctalopia (13 y.o.)

Yes

Group 3

c.[1541T>C(;)9371+1G>C], p.[(Ile514Thr)];[?]

Atrophy RE; Small ring LE

CMO

European

Median (range)

52 (34, 77)

0.24 (−0.10, 2.20)

0.2 (−0.10, 2.20)

24.5 (12, 42)

      
  1. Abbreviations: BE, both eyes; CMO, cystoid macular oedema; FAF, fundus autofluorescence imaging; hyperAF, hyperautofluorescence, IOL, intraocular lens implants; LE, left eye; NA, not applicable; RE, right eye; VA, visual acuity.
  2. *Age at last examination.
  3. aAudiology data: Group 1 good hearing across all frequencies (1A if <40th percentile; 1B if 50–60th percentile); Group 2 marked high-frequency hearing loss compared with low-frequency percentiles; Group 3 atypical/abnormal audiometric configuration without other aetiological explanation. Notably, in subject D2, the audiogram, although abnormal, it was not consistent with Usher syndrome type II. Conversely, subject D23, who reported adult-onset hearing loss, had an audiogram consistent with Usher syndrome type II at age 75 years (see Discussion).
  4. bVariants that are novel to this study are presented in bold. Of these novel changes, only c.3724C>T is found in the ExAC (Exome Aggregation Consortium) browser (3/122810 alleles; accessed 31 December 2014).
  5. Subjects D8, D8a and D8b; subjects D11 and D11a; and subjects D14 and D14a are siblings. Numbering of USH2A variants has been assigned in accordance with NCBI Reference Sequence NM_206933.2.
Back to article page