OMIA 001401-9823 : Waardenburg syndrome, type 2A in Sus scrofa

In other species: golden hamster

Possibly relevant human trait(s) and/or gene(s) (MIM number): 193510

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2016

History: Chen et al. (2016) were the first to describe this animal model of Waardenberg syndrome 2A. It occurs in the Rongchang breed from south-west China.

Inheritance: Chen et al. (2016) summarise their inheritance studies as follows, where "albino" = pigs showing Waardenberg Syndrome 2A: "The deafness incidence rate in offspring of albino × albino mating was 100 %, whereas almost all offspring of normal × albino mating yielded normal hearing offspring. Moreover, there was no significant difference in the prevalence of deafness between males and females. These results implied an autosomal recessive inheritance pattern; to confirm this, 11 pairs of putative heterozygous boars and sows were selected from the normal herd according to the selection criteria of having produced at least one albino offspring. In total, 74 piglets from 11 litters of heterozygous × heterozygous matings were phenotyped to investigate the Mendelian segregation ratio; the results were 25 piglets with hearing loss and 49 piglets with normal hearing. Results of χ2 goodness-of-fit test indicated that the segregating ratio of the hearing loss trait was 3:1 (P < 0.01; . . . ), confirming that the trait’s inheritance mode was autosomal recessive."

Mapping: Chen et al. (2016) "mapped the causative mutant gene of hearing loss to a 763 kb interval (SSC 13: 56,170,062 to 56,933,573)"

Molecular basis: Noting that MITF is the only annotated gene located in the locational candidate region (see Mapping section), and from the results of several functional assays, Chen et al. (2016) eventually concluded that the likely causal variant is a 14bp insertion (g.56482632_56482633insTTTAGTTTAAAAAA) in the upstream non-regulatory region of MITF, which actually created a novel cis-regulatory element (CRE) which, when bound by SOX protein, prevents the transcription of the M isoform of MITF peptide. To the authors' knowledge, "this study provides the first evidence of a de novo CRE in mammals that produces a systemic functional effect."

Clinical features: Chen et al. (2016): "Results from auditory brainstem response (ABR) tests show that the albino pigs produced no recognizable waveforms up to 100 dB sound pressure level (SPL) stimuli in the range from 4–32 kHz, whereas normal pigs produced ABR thresholds at 5–10 dB SPL . . . . Loss of hair cells and stereocilia bundles were observed in the cochleae of the albino pigs by scanning electron microscopy . . . . Because the hearing loss observed in human cases of WS2 is attributed to abnormal cochlear stria vascularis (SV) . . . , the morphology of SV was examined in our study’s albino pigs using light microscopy and transmission electron microscopy (TEM). . . . the albino pigs lacked intermediate cells and had thinner SVs, consisting of two layers of cells only. Because the major functions of the SV are secretion of potassium ions and production of endolymphatic potential (EP), we recorded EPs and measured the [K+] in the scala media of the cochlea. The EP and [K+] were significantly lower than those of normal pigs (P < 0.001, Student’s t-test; . . . ). Since EP and high [K+] in the endolymph are reportedly the driving force for mechanotransduction in cochlear hair cells . . . , a reduction in EP can lead to profound hearing loss. All these phenotypes were tested at postnatal day 13. Thus, these results confirmed the phenotype of profound hearing loss related to cochlear morphology defects in our study’s albino pigs."

Breed: Rongchang.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MITF microphthalmia-associated transcription factor Sus scrofa 13 NC_010455.5 (51177356..51422096) MITF Homologene, Ensembl, NCBI gene


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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Rongchang Waardenburg syndrome, type 2A MITF insertion, small (<=20) 13 g.56482632_56482633insTTTAGTTT 2016 27349893


2016 Chen, L., Guo, W., Ren, L., Yang, M., Zhao, Y., Guo, Z., Yi, H., Li, M., Hu, Y., Long, X., Sun, B., Li, J., Zhai, S., Zhang, T., Tian, S., Meng, Q., Yu, N., Zhu, D., Tang, G., Tang, Q., Ren, L., Liu, K., Zhang, S., Che, T., Yu, Z., Wu, N., Jing, L., Zhang, R., Cong, T., Chen, S., Zhao, Y., Zhang, Y., Bai, X., Guo, Y., Zhao, L., Zhang, F., Zhao, H., Zhang, L., Hou, Z., Zhao, J., Li, J., Zhang, L., Sun, W., Zou, X., Wang, T., Ge, L., Liu, Z., Hu, X., Wang, J., Yang, S., Li, N. :
A de novo silencer causes elimination of MITF-M expression and profound hearing loss in pigs. BMC Biol 14:52, 2016. Pubmed reference: 27349893. DOI: 10.1186/s12915-016-0273-2.

Edit History

  • Created by Frank Nicholas on 18 Oct 2017
  • Changed by Frank Nicholas on 18 Oct 2017