title: Novel splice mutation in microthalmia-associated transcription factor in Waardenburg Syndrome.
abstract: Waardenburg Syndrome (WS) is a syndromic form of hearing loss associated with mutations in six different genes. We identified a large family with WS that had previously undergone clinical testing, with no reported pathogenic mutation. Using linkage analysis, a region on 3p14.1 with an LOD score of 6.6 was identified. Microthalmia-Associated Transcription Factor, a gene known to cause WS, is located within this region of linkage. Sequencing of Microthalmia-Associated Transcription Factor demonstrated a c.1212 G>A synonymous variant that segregated with the WS in the family and was predicted to cause a novel splicing site that was confirmed with expression analysis of the mRNA. This case illustrates the need to computationally analyze novel synonymous sequence variants for possible effects on splicing to maximize the clinical sensitivity of sequence-based genetic testing.
authors: Department of Pediatrics, Columbia University, New York, New York 10032, USA.
authors: Laura
authors: L
authors: Brenner
authors: Kelly
authors: K
authors: Burke
authors: Charles A
authors: CA
authors: Leduc
authors: Saurav
authors: S
authors: Guha
authors: Jiancheng
authors: J
authors: Guo
authors: Wendy K
authors: WK
authors: Chung
mesh_terms: D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005190:Family; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008126:Lod Score; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D012326:RNA Splicing; D017422:Sequence Analysis, DNA; D014849:Waardenburg Syndrome / Q000235:genetics*
chemical_list: C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor