Mercer Stephen, Mutton Patricia, Dahl Hans-Henrik M
Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Melbourne, Australia.
Genet Test Mol Biomarkers. 2011 May;15(5):365-8. doi: 10.1089/gtmb.2010.0177. Epub 2011 Mar 2.
Mutations in the SLC26A4 gene can cause both Pendred syndrome and nonsyndromic enlargement of the vestibular aqueduct, two conditions associated with sensorineural hearing loss. We analyzed the SLC26A4 gene in 44 hearing-impaired patients by nested polymerase chain reaction followed by high-resolution melt analysis. We also used this approach to scan for mutations in KCNJ10 and FOXI1, two genes reported to play a role in the pathogenesis of Pendred syndrome and enlarged vestibular aqueduct. Seven patients with known SLC26A4 mutations were included as controls. All previously identified mutations were detected by high-resolution melt analysis. Of the patients with no known mutations, we detected two SLC26A4 mutations in 5 probands (12%), one mutation in 9 probands (21%), and no mutations in 29 probands (67%). We identified two novel SLC26A4 mutations, p.T485M and p.F718S, and found no evidence of a digenic contribution of KCNJ10 and FOXI1 mutations.
SLC26A4基因的突变可导致 Pendred 综合征和前庭导水管非综合征性扩大，这两种情况都与感音神经性听力损失有关。我们通过巢式聚合酶链反应，随后进行高分辨率熔解分析，对44名听力受损患者的SLC26A4基因进行了分析。我们还使用这种方法扫描了KCNJ10和FOXI1基因中的突变，这两个基因据报道在Pendred综合征和扩大的前庭导水管的发病机制中起作用。7名已知SLC26A4突变的患者作为对照。所有先前鉴定的突变均通过高分辨率熔解分析检测到。在没有已知突变的患者中，我们在5名先证者（12%）中检测到两个SLC26A4突变，在9名先证者（21%）中检测到一个突变，在29名先证者（67%）中未检测到突变。我们鉴定了两个新的SLC26A4突变，p.T485M和p.F718S，并且没有发现KCNJ10和FOXI1突变的双基因贡献的证据。
