Table 1 WFS1 mutations in seven families with Wolfram syndrome

1

F

21

Diabetes at the age of 7, and Hyperuria occurred at the age of 11

double hydronephrosis, bilateral ureteral dilatation, optic nerve papillary atrophy in both eyes.

None

8

c.1314_1317delCTTT

p.F438Lfs*3

Hom

Frameshift

LP(PVS1_Strong + PM2 + PP4)

Novel

2

M

14

Diabetes at the age of 10, slow growth at the age of 11, diminution of vision and incontinentia urinae.at 12

hydronephrosis, bilateral ureal expansion, sensorineural deafness

Parents were consanguineous in marriage. Grandpa, grandma, uncle, and uncle have diabetes

5

c.C529T

p.R177C

Hom

Missense

LP(PM3_Supporting + PM1 + PM2 + PM5 + PP3)

[12]

3

M

17

Diabetes at the age of 3, slow growth at the age of 9, diminution of vision at 14

optic nerve atrophy, mild hydronephrosis in the left kidney, and expansion of the upper ureteric segment

Parents were consanguineous in marriage, and grandpa, grandma and aunt have diabetes.

8

c.C529A

p.R177S

Het

Missense

P(PM1 + PM2 + PM5 + PP1_Strong + PP3 + PP4)

Novel

8

c.G2105A

p.G702D

Het

Missense

P(PM3_Moderate + PM1 + PM2 + PM5 + PP1_Strong + PP3 + PP4)

[13, 14]

4

M

17

Diabetes at the age of 5

optic atrophy, mild hydronephrosis in the left kidney, and expansion of the upper ureteric segment

None

8

c.C1885T

p.R629W

Hom

Missense

LP(PS4 + PM2 + PM3)

Novel

5

M

30

Diminution of vision at 14, diabetes at the age of 16

optic atrophy

Parents denied consanguineous marriage. Uncle have diabetes, and two sisters are diagnosed as WS.

8

c.1859_1860del

p.V620Gfs*91

Het

Frameshift

P(PVS1_Strong + PM2 + PM3 + PP1_Strong + PP4)

Novel

8

c.G2020A

p.G674R

Het

Missense

P(PM3_Strong + PM1 + PM2 + PM5 + PP1_Strong + PP3 + PP4)

[15, 16]

6

M

12

Diabetes at the age of 5

Optic nerve atrophy, and refractive error (both eyes).

Patients were consanguineous in marriage with diabetes, and his brother was also clearly diagnosed as WS.

8

c.C529A

p.R177S

Het

Missense

LP(PM1 + PM2 + PM5 + PP1_Supporting + PP3 + PP4)

Novel

8

c.G2105A

p.G702D

Het

Missense

LP(PM3_Moderate + PM1 + PM2 + PM5 + PP1_Supporting + PP3 + PP4)

[13, 14]

7

M

19

Diabetes at the age of 5

No menstruation

Parents were consanguineous in marriage, and the younger brother was also clearly diagnosed as WS

8

c.G1393C

p.A465P

Hom

Missense

VUS(PM2 + PM3_Supporting + PP4)

Novel