Mutation type*1 |
Mutation position |
Length of affected nucleotides |
Nucleotide sequence after mutation |
Mutation name |
Case # |
Consequence |
Disease |
Position |
Pathological? |
Clinical Feature 1 (Dystopia canthorum) |
Clinical Feature 2 |
Hereditary Pattern |
Ethnic Origin |
Reference |
S |
33+1 |
1 |
A |
33+1G->A |
1 |
ntd 33+1 G-A -> splice doner site change after codon 51, termination in the intron 18 codons downstream |
WS2*2 |
intron 1 (doner site) |
|
Absence of dystopia (The W index was 1.28-1.94, mean 1.68) |
Various combination of hearing loss, heterochromia irides, white forelock and early greying in the affected family members. |
AD*6 |
South Australia |
Tassabehji,M. et al. Nat Genet 8,251(1994) |
S |
442-2 |
1 |
C |
442-2A->C |
1 |
ntd 442-2 A-C -> splice acceptor site change after codon 187, skipping of exon 5, frameshift and termination at the 3' end of exon 6 (position 211) |
WS2 |
intron 4 (acceptor site) |
|
Absence of dystopia (The W index was 1.71-1.98, mean 1.81) |
Hearing loss and white forelock. (All 8 affected family members have sensorineural hearing loss; 3 white forelocks before early greying; 1 white skin patches and 1 heterochromia irides; 3 thin hair. a feature not generally associated with WS) |
AD |
South England |
Tassabehji,M. et al. Nat Genet 8,251(1994) |
S |
33+1 |
1 |
A |
33+1G->A |
1 |
ntd 33+1 G-A -> splice doner site change after codon 51, termination in the intron 18 codons downstream |
WS2 |
intron 1 (doner site) |
|
(Absence of dystopia) |
two of: congenital sensorineural hearing loss, iris pigmentary disturbance, white forelock or greying before age 30 |
AD |
South Australia |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
D |
649 |
3 |
|
649delAGA |
1 |
3-bp del AGA at ntd 649 -> del of Arg at codon 217 |
WS (more resemble Tietz albuminism-deafness syndrome) |
exon 7 (basic domain) |
|
Face was normal and there was no dystopia canthorum. |
severe congenital sensorineural hearing loss, red hair (blond/grey at the age of 16), pale skin with numerous orange freckles, blue eyes and the irides did not transilluminate, but lack of retinal pigmentation. |
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
M |
748 |
1 |
C |
S250P |
1 |
TCC-CCC at ntd 748 -> Ser-Pro at codon 250 |
(unclassified) WS*3 |
exon 8 (helix 2 of HLH) |
|
(insufficient clinical information to judge dystopia) |
unilateral hearing loss and premature greying, shortened fifth fingers and, on the left side, a nail half of which grown black. |
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
M |
832 |
1 |
G |
N278D |
1 |
AAC-GAC at ntd 832 -> Asn-Asp at codon 278 |
WS2 |
exon 8 (ZIP) |
|
(Absence of dystopia) |
sensorial hearing loss and heterochromia. The only relevant family history is that a deceased cousin of the father was said to have had a white forelock in his teens. |
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
M |
892 |
1 |
C |
S298P |
1 |
TCC-CCC at ntd 892 -> Ser-Pro at codon 298 |
WS2 |
exon 9 (3' of ZIP) |
|
(Absence of dystopia) |
two of: congenital sensorineural hearing loss, iris pigmentary disturbance, white forelock or greying before age 30, The family has a 3-generation history of WS2. |
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
P |
-36 |
1 |
A |
-36 G->A |
1 |
G-A transition at position -36 relative to the ATG start codon |
(unclassified) WS |
exon 1 (5'UT) |
Likely non-pathological change |
(insufficient clinical information to judge dystopia) |
Cases with 2 of the hearing or pigmentary criteria for WS1 or 2, but with insufficient clinical information to judge the presence or absence of dystopia |
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
P |
345+13 |
1 |
C |
345+13 G->C |
1 |
ntd 345+13 G-C |
WS (more resemble Tietz albuminism-deafness syndrome) |
intron 3 |
Likely non-pathological change |
|
Individuals or families with auditory and/or pigmentary symptoms probably different from WS, but with no features suggesting wider neural crest involvement. These included families with isolated heterochromia, single individuals with premature greying an |
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
P |
608 |
1 |
A |
R203K |
1 |
AGG-AAG at ntd 608 -> Arg-Lys at codon 203 |
WS2 |
exon 6 (basic domain) |
Likely non-pathological change |
(Absence of dystopia) |
Absence of dystopia plus two of: congenital sensorineural hearing loss, iris pigmentary disturbance, white forelock or greying before age 30, The family has a 4-generation history of typical domain Type 2 WS.
|
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
P |
710+14 |
1 |
G |
710+14 C->G |
1 |
ntd 710+14 C-G |
WS1*4 |
intron 7 |
Likely non-pathological change |
(Dystopia canthorum) |
one of: congenital sensorineural haring loss >25 dB, iris pigmentary abnormality (excluding blue eyes in white persons), white forelock |
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
P |
710+28 |
1 |
C |
710+28 T->C |
1 |
ntd 710+28 T-C |
(unclassified) WS |
intron 7 |
Likely non-pathological change |
(insufficient clinical information to judge dystopia) |
Cases with 2 of the hearing or pigmentary criteria for WS1 or 2, but with insufficient clinical information to judge the presence or absence of dystopia |
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
P |
710+28 |
1 |
C |
710+28 T->C |
1 |
ntd 710+28 T-C |
WS2 |
intron 7 |
Likely non-pathological change |
(Absence of dystopia) |
two of: congenital sensorineural hearing loss, iris pigmentary disturbance, white forelock or greying before age 30 |
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
P |
710+31 |
1 |
C |
710+31 T->C |
1 |
ntd 710+31 T-C |
(probable) WS2*5 |
intron 7 |
Likely non-pathological change |
|
The family history showed hearing loss plus one or more WS2 criteria, in a pattern compatible with dominant inheritance, but no one individual had more than one feature |
AD |
ND |
Tassabehji,M. et al. Hum Mol Genet 4,2131(1995) |
N |
640 |
1 |
T |
R214X |
1 |
CGA-TGA at ntd 640 -> Arg-Stop at codon 214, trancated protein lacking HLH-Zip structure |
WS2 |
exon 7 |
|
None of the family members showed dystopia canthorum. |
sensori-neural hearing loss, heterochromia irides, white forelock, and early graying. |
AD |
Nothrn European |
Nobukuni,V. et al. Am J Hum Genet 59,76(1996) |
N |
775 |
1 |
T |
R259X |
1 |
CGA-TGA at ntd 775 -> Arg-Stop at codon 259, trancated protein lacking Zip structure |
WS2 |
exon 8 |
|
None of the family members showed dystopia canthorum. |
sensori-neural hearing loss, heterochromia irides, white forelock, and early graying. |
AD |
various |
Nobukuni,V. et al. Am J Hum Genet 59,76(1996) |
N |
640 |
1 |
T |
R214X |
1 |
CGA-TGA at ntd 640 -> Arg-Stop at codon 214, trancated protein lacking HLH-Zip |
WS2 |
exon 7 |
|
absent of dystopia conthorum (W index <2.07) |
sensorineural hearing loss, heterochromia iridis, premature graying and white forelock. |
AD |
South India |
Lalwani, AK. Et al. Am J Med Genet 80, 406(1998) |
FD |
824 |
1 |
|
824delA |
1 |
1-bp del A at ntd 824 (codon 275) -> frameshift and a TGA termination in exon 9 |
WS2 |
exon 8 |
|
|
The affected individuals were also either homozygous or heterozygous for the arg402-to-gln polymorphism of the tyrosinase gene(TYR). TYR gene is controlled by the MITF. |
AD |
various*7 |
Morell, R. et al. Hum Mol Genet 6, 659(1997) |