@article {152,
	title = {Rare A2ML1 variants confer susceptibility to otitis media.},
	journal = {Nat Genet},
	volume = {47},
	year = {2015},
	month = {2015 Aug},
	pages = {917-20},
	abstract = {<p>A duplication variant within the middle ear-specific gene A2ML1 cosegregates with otitis media in an indigenous Filipino pedigree (LOD score = 7.5 at reduced penetrance) and lies within a founder haplotype that is also shared by 3 otitis-prone European-American and Hispanic-American children but is absent in non-otitis-prone children and >62,000 next-generation sequences. We identified seven additional A2ML1 variants in six otitis-prone children. Collectively, our studies support a role for A2ML1 in the pathophysiology of otitis media. </p>},
	keywords = {alpha-Macroglobulins, Animals, Base Sequence, Child, Cochlea, Exome, Family Health, Female, Gene Duplication, Gene Frequency, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Male, Mice, Inbred C57BL, Models, Molecular, Otitis Media, Pedigree, Principal Component Analysis, Protein Conformation, Sequence Analysis, DNA},
	issn = {1546-1718},
	doi = {10.1038/ng.3347},
	author = {Santos-Cortez, Regie Lyn P and Chiong, Charlotte M and Reyes-Quintos, Ma Rina T and Tantoco, Ma Leah C and Wang, Xin and Acharya, Anushree and Abbe, Izoduwa and Giese, Arnaud P and Smith, Joshua D and Allen, E Kaitlynn and Li, Biao and Cutiongco-de la Paz, Eva Maria and Garcia, Marieflor Cristy and Llanes, Erasmo Gonzalo D V and Labra, Patrick John and Gloria-Cruz, Teresa Luisa I and Chan, Abner L and Wang, Gao T and Daly, Kathleen A and Shendure, Jay and Bamshad, Michael J and Nickerson, Deborah A and Patel, Janak A and Riazuddin, Saima and Sale, Michele M and Chonmaitree, Tasnee and Ahmed, Zubair M and Abes, Generoso T and Leal, Suzanne M}
}
@article {299,
	title = {Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89.},
	journal = {Am J Hum Genet},
	volume = {93},
	year = {2013},
	month = {2013 Jul 11},
	pages = {132-40},
	abstract = {<p>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{\textquoteright} 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. </p>},
	keywords = {Animals, Case-Control Studies, Chickens, Cochlea, Computational Biology, Consanguinity, Female, Genetic Linkage, Hair Cells, Auditory, Inner, Haplotypes, Hearing Loss, Homozygote, Humans, Lysine-tRNA Ligase, Male, Mice, Mutation, Missense, Pedigree, Transfer RNA Aminoacylation, Zebrafish},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2013.05.018},
	author = {Santos-Cortez, Regie Lyn P and Lee, Kwanghyuk and Azeem, Zahid and Antonellis, Patrick J and Pollock, Lana M and Khan, Saadullah and Andrade-Elizondo, Paula B and Chiu, Ilene and Adams, Mark D and Basit, Sulman and Smith, Joshua D and Nickerson, Deborah A and McDermott, Brian M and Ahmad, Wasim and Leal, Suzanne M}
}
