@article {730,
	title = {Hearing impairment locus heterogeneity and identification of PLS1 as a new autosomal dominant gene in Hungarian Roma.},
	journal = {Eur J Hum Genet},
	volume = {27},
	year = {2019},
	month = {2019 Jun},
	pages = {869-878},
	abstract = {<p>Roma are a socially and culturally distinct isolated population with genetically divergent subisolates, residing mainly across Central, Southern, and Eastern Europe. We evaluated the genetic etiology of hearing impairment (HI) in 15 Hungarian Roma families through exome sequencing. A family with autosomal dominant non-syndromic HI segregating a rare variant in the Calponin-homology 2 domain of PLS1, or Plastin 1 [p.(Leu363Phe)] was identified. Young adult Pls1 knockout mice have progressive HI and show morphological defects to their inner hair cells. There is evidence that PLS1 is important in the preservation of adult stereocilia and normal hearing. Four families segregated the European ancestral variant c.35delG [p.(Gly12fs)] in GJB2, and one family was homozygous for p.(Trp24*), an Indian subcontinent ancestral variant which is common amongst Roma from Slovakia, Czech Republic, and Spain. We also observed variants in known HI genes USH1G, USH2A, MYH9, MYO7A, and a splice site variant in MANBA (c.2158-2A>G) in a family with HI, intellectual disability, behavioral problems, and respiratory inflammation, which was previously reported in a Czech Roma family with similar features. Lastly, using multidimensional scaling and ADMIXTURE analyses, we delineate the degree of Asian/European admixture in the HI families understudy, and show that Roma individuals carrying the GJB2 p.(Trp24*) and MANBA c.2158-2A>G variants have a more pronounced South Asian background, whereas the other hearing-impaired Roma display an ancestral background similar to Europeans. We demonstrate a diverse genetic HI etiology in the Hungarian Roma and identify a new gene PLS1, for autosomal dominant human non-syndromic HI.</p>},
	issn = {1476-5438},
	doi = {10.1038/s41431-019-0372-y},
	author = {Schrauwen, Isabelle and Melegh, B{\'e}la I and Chakchouk, Imen and Acharya, Anushree and Nasir, Abdul and Poston, Alexis and Cornejo-Sanchez, Diana M and Szabo, Zsolt and Karosi, Tam{\'a}s and Bene, Judit and Melegh, B{\'e}la and Leal, Suzanne M}
}
@article {664,
	title = {Heterozygosity mapping for human dominant trait variants.},
	journal = {Hum Mutat},
	volume = {40},
	year = {2019},
	month = {2019 07},
	pages = {996-1004},
	abstract = {<p>Homozygosity mapping is a well-known technique to identify runs of homozygous variants that are likely to harbor genes responsible for autosomal recessive disease, but a comparable method for autosomal dominant traits has been lacking. We developed an approach to map dominant disease genes based on heterozygosity frequencies of sequence variants in the immediate vicinity of a dominant trait. We demonstrate through theoretical analysis that DNA variants surrounding an inherited dominant disease variant tend to have increased heterozygosity compared with variants elsewhere in the genome. We confirm existence of this phenomenon in sequence data with known dominant pathogenic variants obtained on family members and in unrelated population controls. A computer-based approach to estimating empirical significance levels associated with our test statistics shows genome-wide p-values smaller than 0.05 for many but not all of the individuals carrying a pathogenic variant.</p>},
	issn = {1098-1004},
	doi = {10.1002/humu.23765},
	author = {Imai-Okazaki, Atsuko and Li, Yi and Horpaopan, Sukanya and Riazalhosseini, Yasser and Garshasbi, Masoud and Mosse, Yael P and Zhang, Di and Schrauwen, Isabelle and Sharma, Aarushi and Fann, Cathy S J and Leal, Suzanne M and Lathrop, Mark and Ott, Jurg}
}
