Actas de congresos
Novel mutations of PAX3, MITF and SOX10 genes found in Waardenburg syndrome types 1 and 2 in Brazilian patients
Fecha
2013-09-16Registro en:
Congresso Brasileiro de Genética, 59., p. 75, 2013, Águas de Lindóia, São Paulo.
978-85-89109-06-2
Autor
Bocangel, Magnolia Astrid Pretell
Netto, Regina Celia Mingroni
Otto, Paulo Alberto
Institución
Resumen
Waardenburg syndrome (WS) is a dominant inherited disorder characterized by pigmentary abnormalities of the skin
and iris (heterochromia or hypochromia irides) associated with sensorial hearing loss and cranio-facial dysmorphisms.
Most cases of WS fall into two distinct autosomal dominant forms, WS1 and WS2. Dystopia canthorum is present
in almost all a ected individuals with WS1 and absent in all patients with the WS2 variant. e prevalence of
WS (including two other variants rarely found) is estimated in about 1: 40,000; among deaf individuals WS is
responsible for about three percent of cases in which the deafness is congenital. WS1 is caused by PAX3 mutations,
while MITF and SOX10 mutations are associated with type WS2. All these genes play an important role in the
migration and di erentiation of melanocytes, pigment-producing cells that originate from the embryonic neural
crest. We have investigated a sample of 47 WS patients (most are clinically described in Pardono E et al., Amer.
J. Med. Genet. 117A: 223-235, 2003) with hearing loss, from which 12 were classi ed as WS1 and six as WS2,
while 29 were isolated cases without telecanthus, very likely a ected by WS2. We report six mutations that were
found in the PAX3 gene, from which three are novel and three had already been reported in the literature; one
novel mutation in MITF gene; and three novel mutations in the SOX10 gene. Bioinformatic tools indicate that
all novel mutations we found are probably pathogenic. On the basis of these ndings, we conclude that molecular
testing and the exact interpretation of the e ect of mutations found in WS is of signi cant importance to genetic
counseling, since the probability of developing sensorial hearing loss is much higher in WS2 than in WS1.