A novel KIT mutation in a family with expanded syndrome of piebaldism

Hamadah, Issam; Chisti, Muzamil; Haider, Mansoor A.; Dosssari, Haya Al; Alhumaidan, Rawan; Meyer, Brian F.; Wakil, Salma M.

doi:10.1016/j.jdcr.2019.01.021

Cited by 6 publications

(13 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6a). Moreover, only R796G induced congenital and profound hearing loss in offspring (Spritz & Beighton, 1998), while A608D induced unilateral deafness in only one patient (Hamadah et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Until 1998, Spritz et al firstly described the pathogenicity of heterozygous c-KIT (p.R796G) in piebaldism with congenital deafness (Spritz & Beighton, 1998). Recently, the homozygous deletion of exons 20 and 21 inc-KIT was reported to induce piebaldism and deafness in humans (Kilsby et al, 2013), and the heterozygous mutation of A608D was found in one adult patient with non-hereditary unilateral deafness (Hamadah et al, 2019). Furthermore, several KIT mutations (KIT W-V , KIT Wads , and KIT F856S ) have been identified in mice with hypopigmentation and hearing loss (Hoshino et al, 2000;J.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, the low and irregular coincidence of piebaldism with hearing loss seemed to be an expanded and occasional manifestation of c-KIT mutations. Thus, piebaldism was speculated as an inherited condition in an intermediate rather than a dominant manner (Hamadah et al, 2019;Spritz & Beighton, 1998).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of a novel c-KIT mutation inducing piebaldism and hearing loss in pigs by ENU mutagenesis

Lin

Guo

et al. 2020

Preprint

View full text Add to dashboard Cite

As a rare autosomal dominant hypopigmentation disease, piebaldism is characterized by the presence of patchy albinism on the skin, and is mainly caused by the loss-of-function mutations in c-KIT gene. Congenital hearing loss is occasionally found as an expanded syndrome of piebaldism. However, the correlation between c-KIT mutations and piebaldism with hearing loss has not yet been described. Herein, we created a mutant strain of miniature pig through the N-ethyl-N-nitrosourea (ENU)-mediated mutagenesis, which showed severe piebaldism and congenital profound hearing loss. A genome-wide association study (GWAS) linked these phenotypes to the c.2430T>A transition mutation in exon 17 of c-KIT, resulting in an Asp810Glu substitution in the tyrosine kinase domain. The Asp810 was localized at the highly conserved DFG motif and the transition from Asp to Glu would deplete the kinase activity of c-KIT protein, finally inducing the degeneration of intermediate cells and hair cells in inner ear. The c-KIT c.2430T>A/+ pig is the first large animal model with a c-KIT loss-of-function mutation, showing piebaldism with hereditary hearing loss. It will serve as an experimental model for exploring the function of c-KIT during biological processes and the candidate therapies for c-KIT mutations related diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of a novel c-KIT mutation inducing piebaldism and hearing loss in pigs by ENU mutagenesis

Lin

Guo

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Previous studies have implied that neurogenic factors may induce skin diseases or accelerate disease progression [ 11 – 13 ]. Dysregulation in differentiation, development, and melanocytes' activity can cause a series of skin pigmented diseases, such as generalized dyschromatopsia and mottle disease [ 14 , 15 ]. Whether Fam114A1 is involved in the development and functional regulation of melanocytes has yet to be reported.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Fam114A1 protects melanocytes from apoptosis through higher RACK1 expression

Zhou

Lin

et al. 2021

Aging

View full text Add to dashboard Cite

Fam114A1 is a gene closely related to the development of nerve cells, melanocytes, and nerve cells that originate from the neural crest of the embryonic ectoderm. Recent studies showed that Fam114A1 has a role in the occurrence of ankylosing myelitis spondylitis and autoimmune enteritis; still, its cellular function remains poorly understood. In this study, we investigated the effect of Fam114A1 on the biological activity of melanocytes. We found that the expression of Fam114A1 in vitiligo melanocytes (MCV-L, MCV-N, PI3V) was higher than that in normal melanocytes, and the biological function of melanocytes was significantly affected when the Fam114A1 gene was silenced. Inhibition of Fam114A1 increased proliferation, migration, and melanin synthesis proteins, decreased apoptosis, while its overexpression reversed this process. Mechanistically, we discovered that RACK1 is a target protein of Fam114A1 and that RACK1 can be negatively regulated by Fam114A1. Further study showed that Fam114A1 inhibition could not protect melanocytes from apoptosis once the expression of RACK1 protein was silenced. In summary, Fam114A1 is an effective regulatory protein for regulating the function of melanocytes. Inhibition Fam114A1 protects melanocytes from apoptosis through increasing RACK1.

show abstract

“…KIT-KITLG signaling pathway and MITF were suggested to mutually interact in the migration process of melanocyte from the neural crest to stria vascularis (SV). The imbalanced migration and distribution of melanocytes in stria vascularis might be cause by laterality of hearing (Zazo Seco et al, 2015;Hamadah et al, 2019). However, most cases of CSSD in the clinic were non-syndromic and reported to be not correlated with other systematic symptoms.…”

Section: Introductionmentioning

confidence: 99%

A Porcine Congenital Single-Sided Deafness Model, Its Population Statistics and Degenerative Changes

Ren

Zheng

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

ObjectiveTo describe and study the population statistics, hearing phenotype, and pathological changes of a porcine congenital single-sided deafness (CSSD) pedigree.MethodsClick auditory brainstem response (ABR), full-frequency ABR, and distortion product otoacoustic emission (DPOAE) were used to assess the hearing phenotype of the strain. Tympanogram was used to assess the middle ear function since birth. Celloidin embedding–hematoxylin–eosin (CE-HE) stain and scanning electron microscopy (SEM) were used to study the pathological changes of cochlear microstructures. Chi-square analysis was used to analyze the relation between hearing loss and other phenotypes.ResultsThe mating mood of CSSD with CSSD was most efficient in breeding-targeted CSSD phenotype (47.62%), and the prevalence of CSSD reached 46.67% till the fifth generation, where 42.22% were bilateral hearing loss (BHL) and 9.00% were normal hearing (NH) individuals. Hearing loss was proved to have no relation with coat color (P = 0.0841 > 0.05) and gender (P = 0.4621 > 0.05) by chi-square analysis. The deaf side of CSSD offspring in the fifth generation had no relation with that of their maternal parent (P = 0.2387 > 0.05). All individuals in this strain exhibited congenital severe to profound sensorineural hearing loss with no malformation and dysfunction of the middle ear. The good hearing ear of CSSD stayed stable over age. The deaf side of CSSD and BHL presented cochlear and saccular degeneration, and the hair cell exhibited malformation since birth and degenerated from the apex to base turn through time. The pathology in BHL cochlea progressed more rapidly than CSSD and till P30, the hair cell had been totally gone. The stria vascularis (SV) was normal since birth and degenerated through time and finally exhibited disorganization of three layers of cells.ConclusionThis inbred porcine strain exhibited high and stable prevalence of CSSD, which highly resembled human non-syndromic CSSD disease. This porcine model could be used to further explore the etiology of CSSD and serve as an ideal tool for the studies of the effects of single-sided hearing deprivation on neural, cognitive, and behavioral developments and the benefits brought by CI in CSSD individuals.

show abstract

A novel KIT mutation in a family with expanded syndrome of piebaldism

Cited by 6 publications

References 12 publications

Identification of a novel c-KIT mutation inducing piebaldism and hearing loss in pigs by ENU mutagenesis

Identification of a novel c-KIT mutation inducing piebaldism and hearing loss in pigs by ENU mutagenesis

Inhibition of Fam114A1 protects melanocytes from apoptosis through higher RACK1 expression

A Porcine Congenital Single-Sided Deafness Model, Its Population Statistics and Degenerative Changes

Contact Info

Product

Resources

About