DFNB89, a novel autosomal recessive nonsyndromic hearing impairment locus on chromosome 16q21-q23.2

Basit, Sulman; Lee, Kwanghyuk; Habib, Rabia; Chen, Leon; Umm-e-Kalsoom,; Santos‐Cortez, Regie Lyn P.; Azeem, Zahid; Andrade, Paula B.; Ansar, Muhammad; Ahmad, Wasim

doi:10.1007/s00439-010-0934-0

Cited by 11 publications

(6 citation statements)

References 21 publications

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“…The highest PPLD score (0.08) in the region was obtained at rs7188225 between the cadherin 5, type 2 (CDH5) gene and LOC28386 . Interestingly, the region has also been pinpointed in autosomal recessive nonsyndromic hearing impairment 39 . Furthermore, the COMB scores were linked to 18q12.3-21.1 (PPL=0.55, Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions

et al. 2014

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Humans have developed the perception, production and processing of sounds into the art of music. A genetic contribution to these skills of musical aptitude has long been suggested. We performed a genome-wide scan in 76 pedigrees (767 individuals) characterized for the ability to discriminate pitch (SP), duration (ST) and sound patterns (KMT), which are primary capacities for music perception. Using the Bayesian linkage and association approach implemented in program package KELVIN, especially designed for complex pedigrees, several SNPs near genes affecting the functions of the auditory pathway and neurocognitive processes were identified. The strongest association was found at 3q21.3 (rs9854612) with combined SP, ST and KMT test scores (COMB). This region is located a few dozen kilobases upstream of the GATA binding protein 2 (GATA2) gene. GATA2 regulates the development of cochlear hair cells and the inferior colliculus (IC), which are important in tonotopic mapping. The highest probability of linkage was obtained for phenotype SP at 4p14, located next to the region harboring the protocadherin 7 gene, PCDH7. Two SNPs rs13146789 and rs13109270 of PCDH7 showed strong association. PCDH7 has been suggested to play a role in cochlear and amygdaloid complexes. Functional class analysis showed that inner ear and schizophrenia related genes were enriched inside the linked regions. This study is the first to show the importance of auditory pathway genes in musical aptitude.

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Section: Resultsmentioning

confidence: 99%

A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions

et al. 2014

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“…A region of chromosome 16 contains a deafness locus where there are two candidate genes, cadherin type 5 ( CDH5 ), and LOC283867. Cadherin type 23 ( CDH23 ) and PCDH15 are crucial as they are physically connected to each other in sensory hair cells , and have been reported to cause hearing loss in mice .…”

Section: Genome‐wide Linkage and Association Analysesmentioning

confidence: 99%

Genomics approaches to study musical aptitude

Oikkonen

Järvelä

2014

BioEssays

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Although music and other forms of art can develop in diverse directions, they are linked to the genetic profiles of populations. Hearing music is a strong environmental trigger that serves as an excellent model to study the crosstalk between genes and the environment. We propose that the ability to enjoy and practice music requires musical aptitude, which is a common and innate trait facilitating the enjoyment and practice of music. The innate drive for music can only have arisen by exposure to music, and it develops with motivation and training in musically rich environments. Recent genomic approaches have shown that the genes responsible for inner ear development, auditory pathways and neurocognitive processes may underlay musical aptitude. It is expected that genomic approaches can be applied to musical traits and will reveal new biological mechanisms that affect human evolution, brain function, and civilisation.

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“…On the other hand, KARS showed weak localization to the stria vascularis, Reissner's membrane, and cochlear nerve endings (Figure 3G). In this report, three ARNSHI-affected families that segregate different haplotypes overlapping within the DFNB89 interval 6 were found to each have a missense mutation within KARS, which encodes a ubiquitously expressed protein, lysyl-tRNA synthetase (UniGene 131351 -Hs.3100). Many genes that are involved in the etiology of ARNSHI also encode ubiquitously expressed proteins, e.g., ESRRB (DFNB35), 35 HGF (DFNB39), 36 ILDR1 (DFNB42), 37 and MSRB3 (DFNB74) 38 to name a few.…”

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confidence: 95%

“…Previously, an ARNSHI-associated locus, DFNB89, was mapped to chromosomal region 16q21-q23.2 in two unrelated, consanguineous Pakistani families. 6 The two families, 4338 and 4406 (Figures 1A and 1B), had maximum multipoint LOD scores of 6.0 and 3.7, respectively. The homozygosity regions that overlap in the two families led to the identification of a 16.1 Mb locus (chr16: 63.6-79.7 Mb) that includes 180 genes.…”

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confidence: 98%

Mutations in KARS, Encoding Lysyl-tRNA Synthetase, Cause Autosomal-Recessive Nonsyndromic Hearing Impairment DFNB89

Santos‐Cortez

Lee

Azeem

et al. 2013

The American Journal of Human Genetics

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Previously, DFNB89, a locus associated with autosomal-recessive nonsyndromic hearing impairment (ARNSHI), was mapped to chromosomal region 16q21-q23.2 in three unrelated, consanguineous Pakistani families. Through whole-exome sequencing of a hearing-impaired individual from each family, missense mutations were identified at highly conserved residues of lysyl-tRNA synthetase (KARS): the c.1129G>A (p.Asp377Asn) variant was found in one family, and the c.517T>C (p.Tyr173His) variant was found in the other two families. Both variants were predicted to be damaging by multiple bioinformatics tools. The two variants both segregated with the nonsyndromic-hearing-impairment phenotype within the three families, and neither mutation was identified in ethnically matched controls or within variant databases. Individuals homozygous for KARS mutations had symmetric, severe hearing impairment across all frequencies but did not show evidence of auditory or limb neuropathy. It has been demonstrated that KARS is expressed in hair cells of zebrafish, chickens, and mice. Moreover, KARS has strong localization to the spiral ligament region of the cochlea, as well as to Deiters' cells, the sulcus epithelium, the basilar membrane, and the surface of the spiral limbus. It is hypothesized that KARS variants affect aminoacylation in inner-ear cells by interfering with binding activity to tRNA or p38 and with tetramer formation. The identification of rare KARS variants in ARNSHI-affected families defines a gene that is associated with ARNSHI.

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DFNB89, a novel autosomal recessive nonsyndromic hearing impairment locus on chromosome 16q21-q23.2

Cited by 11 publications

References 21 publications

A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions

A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions

Genomics approaches to study musical aptitude

Mutations in KARS, Encoding Lysyl-tRNA Synthetase, Cause Autosomal-Recessive Nonsyndromic Hearing Impairment DFNB89

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