TABLE I.

Clinical Manifestations in Eight Probands

Family	KW200128a	NSDF916	NSDF1272	NSDF2032	NSDF1865	81	KW010862	NSDF1793
Proband ID	KW200128-VI:5	916-IV:10	1272-IV:2	2032-IV:4	1865-II:4	Fam81-III:1	KW01862-IV:1	1793-III:1
Inheritance	ADOA + HI	ADOA + HI	ADOA + HI	ADOA + HI	ADOA + HI	Possibly sporadic	ADOA + HI	ADOA + HI
Age	Deceased age 63	32	38	54	46	55	14	49
Nationality	Swedish	US/Caucasian	US/Caucasian	US/Caucasian	US/Caucasian	US/Caucasian	UK	US
Phenotype	OA + HI	OA + HI	OA + HI	OA + HI	OA + HI	OA + HI	OA + HI	OA + HI
WFS1 Mutation	p.A684V	p.A684V	p.A684V	p.A684V	p.A684V	p.A684V	p.G780S	p.D797Y
Optic atrophy
Age of onset (years)	9	- Diagnosed at age 26)	- Diagnosed at age 30)	16	11 (Diagnosed at age 16)	- Diagnosed at age 41)	12	20
Visual acuity	20/40 (R) 20/40 (L)	20/40(R) 20/32 (L)	-	-	20/30 (R) 20/30 (L)	20/60 (R) 20/60 (L)	20/25 (R) 23/25 (L)	20/80 (R) 20/70 (L)
Colour vision	-	Abnormal colour vision test (Ishihara plates)	-	-	Normal	-	Reduced	Not reported night and colour vision problems
Optic discs / optic nerves	Pale	Pale optic discs and cupped to 0.8	-	-	Extreme pallor of optic discs with hypoplasia of the vessels and cupped to 0.7	Extreme pallor of optic nerves	Bilateral pallor of optic nerves	Some pallor of the discs and narrowing of the vessels. Pale optic nerves bilaterally
Hearing impairment
Age of onset (years)	Early childhood	Congenital	Early childhood	Congenital	1.5y	3y	Congenital	3–4y
Severity	Severe, progressive	Severe to profound	Profound, progressive	?	Severe to profound	Profound	Profound	Severe to profound, progressive
Diabetes	-	No	-	-	No	No	No	No
Psychiatric abnormalities	Depression, hallucinationsb	-	-	-	Depression	-	No	No
Other disorders / symptoms	-	-	-	-	Developed diabetes insipidus at age 20 following hypophysectomy for suspected pituitary tumor	-	No	No
Additional Information	Myopia in one family member	Humphrey visual fields with small enlargement of blind spot bilaterally. Retinal vessels, macula and retina periphery otherwise normal	Daughter with OA, normal hearing and bipolar illness does not have the mutation	GJB2 c.35delG homozygote	As part of evaluation for OA she had a CT scan. Mother is deaf from congenital rubella syndrome. Eye pressure 10 and 12 mm. Father is deaf, have OA and reported to have problems with colour vision	Has a son and a daughter with Wolfram syndrome and two WFS1 mutations: p.V415del and p.A684V c	Normal p-glucose and urine osmolality. Maternal great aunt with psychosis	OA was confirmed by CT/MRI scan. Except from deafness and OA physical examination normal. Eye pressure 10 and 12 mm. Normal macula and no evidence for retinal dystrophy. Also no diabetes in the mother of the proband who is deaf and has OA

ADOA = autosomal dominant optic atrophy; HI = Hearing impairment; (−) No information; y = years;

^athe symptoms of the affected individuals have previously been described in Swedish (Samuelson, 1940);

^bsome affected family members have anxiety and one affected family member (VII:5) committed suicide;

^cThe p.V415del mutation in the children is inherited from their mother (the mutations are listed in the Kresge/WFS1 database);

mm = millimetres of mercury