Genotype and phenotype of all Waardenburg syndrome index patients
| Index patient | Mutation description | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age | Gender | Gene | Gene structure affected | Nucleotide level | Protein level | Type | Transmission mode | Dystopia canthorum | Heterochromia iridis | Hearing loss | Other clinical symptoms | Notes | |
| 1 | 6.5 years | m | PAX3 | Exon 2 | c.111dupC | p.Val38Argfs*76 | Insertion | n.a. | + | + | (+) | Synophrys, low frontal and nuchal hairline, skin hyperpigmentation anomalies | – |
| 2 | 7 years | f | PAX3 | Exon 2 | c.143G>A | p.Gly48Asp | Missense | Maternal | + | − | + | High nasal bridge, synophrys, eyebrow flaring, skin depigmentation; affected family members with premature greying and dystopia canthorum | Different amino acid change at same position described in ref. 22 |
| 3 | 3 years | f | PAX3 | Exon 2 | c.186G>A | p.Met62Ile | Missense | Paternal | + | + | ++ | – | Different amino acid change at same position: described in ref. 23 |
| 4 | 34 years | m | PAX3 | Exon 3 | c.400C>T | p.Arg134X | Non-sense | n.a. | + | + | − | – | – |
| 5 | 6 months | m | PAX3 | Exon 5 | c.589delT | p.Ser197Leufs*19 | Deletion | Paternal | + | − | + | White forelock | – |
| 6 | 3 months | m | PAX3 | Exon 5 | c.655C>T | p.Gln219X | Non-sense | Paternal | + | + | − | High nasal bridge | – |
| 7 | 17 months | m | PAX3 | Exon 5 | c.784C>T | p.Arg262X | Non-sense | Maternal | + | + | + | White forelock, synophrys, high nasal bridge, prognathia, hypopigmentation anomalies | Described in ref. 24 |
| 8 | 1 week | m | PAX3 | Intron 5 | c.793-1G>T | – | Splice site | De novo | + | − | − | White forelock, craniofacial dysmorphism | – |
| 9 | 17 months | m | PAX3 | Exon 6 | c.946_956del | p.Ile317Cysfs*89 | Deletion | n.a. | + | − | + | Unilateral hearing loss | – |
| 10 | 2,5 years | m | PAX3 | Exon 6 | c.955C>T | p.Gln319X | Non-sense | n.a. | + | + | ++ | High nasal bridge, mild skin depigmentation | – |
| 11 | n.a. | m | MITF | Exon 1 | [c.28T>A;c.33+6del7] | p.Tyr10Asn | Missense/deletion | Paternal | − | + | + | – | – |
| 12 | 16 years | m | MITF | Exon 3 | c.328C>T | p.Arg110X | Non-sense | n.a. | − | + | + | – | – |
| 13 | 7 months | m | MITF | Exon 7 | c.650G>T | p.Arg217Ile | Missense | De novo | − | − | + | Blue eyes with hypoplasia of iris stroma, white forelock | Described in ref. 25 |
| 14 | 23 years | m | PAX3 | Entire gene | c.(?_-61)_(1452-33_?) | – | Deletion entire gene | Paternal | + | − | + | Pigmentation anomalies, unilateral hearing loss | Described in ref. 26 |
| 15 | 42 years | m | PAX3 | Exon 7 | c.958+?_1174-?del | – | Deletion exon 7 | n.a. | + | − | + | Pigmentation anomalies | – |
| 16 | 6 years | f | PAX3 | Exons 8–9 | c.1173+?_(1452-33_?)del | – | Deletion exons 8–9 | n.a. | + | − | + | Blue eyes, synophrys, medial eyebrow flaring | – |
| 17 | 5 months | f | PAX3 | Entire gene | c.(?_-61)_(1452-33_?) | – | Deletion entire gene | n.a. | + | + | + | Unilateral hearing loss | Described in ref. 26 |
| 18 | 7 years | m | MITF | 5′-UTR region | c.?_1-70453dup | – | Duplication | n.a. | − | − | (+) | – | – |
| 19 | 3 years | m | MITF | Exons 1–9 | c.1-70433_?_(988_?)del | – | Deletion exons 1–9 | De novo | − | + | + | Bilateral hearing loss | – |
‘De novo’, under consideration of provided information concerning kinship, no paternity testing was performed.
f, female; m, male; (+), mild; +, moderate; ++, severe; n.a., not available.