| First Author | Smith SD | Year | 1997 |
| Journal | Am J Hum Genet | Volume | 61 |
| Issue | Suppl (2033) | Pages | A347 (Abstr.) |
| Mgi Jnum | J:48352 | Mgi Id | MGI:1267241 |
| Citation | Smith SD, et al. (1997) Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF. Am J Hum Genet 61(Suppl (2033)):A347 (Abstr.) |
| abstractText | Full text of Abstract: 2033. Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF. S.D. Smith, J.B. Kenyon, P.M. Kelley, D. Hoover, B. Comer. Boys Town National Research Hospital, Omaha, NE. In 1963, W. Tietz described an autosomal dominant syndrome of hypopigmentation and deafness (MIM 103500). There were no further reports of this syndrome and Reed et al. (1967) suggested that the co-occurance of the two features were coincidental. We have re-ascertained this family, and confirmed the existence of the syndrome through at least 4 generations. All affected individuals are born "snow white", but gradually gain some pigmentation, with fair skin and blond hair. Eyebrows and eyelashes remain blond. Eyes are blue, with albinoid fundi, but no nystagmus or other visual problems. Craniofacial appearance is normal. Hearing loss is always bilateral, congenital, and profound, and communication is primarily through signing. There is no variation in expression and penetrance is complete. Significant linkage was found in the region of MITF (microphthalmia-associated transcription factor), which is known to cause Waardenburg syndrome type 2A (WS2A). WS2A is characterized by patches of depigmentation distinctive craniofacial appearance heterchromnia, and hearing loss, with variation in expression and penetrance for all features. A unique heterduplex pattern of exons 5 and 6 of MITF was found to segregate with affected members of the kindred. Sequence analysis of these exons and the flanking intron-exon junctions found a CG to GC transversion i n both. The change bordering exon 5 was adjacent to the splice junction consensus sequence. The change in exon 6 resulted in a change from Asparagine to Lysine at amino acid 207 in the basic region of this transcription factor. The second change may disrupt the normal DNA binding properties of this gene product. A different mutation of this gene was reported to cause a phenotype distinct from WS2A and somewhat similar to Tietz syndrome in a mother and son. (Tassabehji et al., 1995). (Supported by NIH-NIDCD P60 DC00982) |
