SHORT COMMUNICATION A Gene for Recessive Nonsyndromic Sensorineural Deafness (DFNB18) Maps to the Chromosomal Region 11p14–p15.1 Containing the Usher Syndrome Type 1CGene Pawan K. Jain,* ,1 Anil K. Lalwani,† Xiaoyan C. Li,* Teresa L. Singleton,* Tenesha N. Smith,* Achih Chen,‡ Dilip Deshmukh,§ Ishwar C. Verma, ¶ Richard J. H. Smith,‡ and Edward R. Wilcox* ,2 * Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, Maryland 20850-3227; †Division of Otology, Neurotology, and Skullbase Surgery, Department of Otolaryngology, Head and Neck Surgery, School of Medicine, University of California, San Francisco A730, 400 Parnassus Avenue, San Francisco, California 94143; ‡Molecular Otolaryngology Research Laboratories, Department of Otolaryngology - Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242-1078; §Deshmukh Nursing Home, Sangram Chouk, Ichalkaranji, 416 115 Maharashtra State, India; and ¶ All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India Received January 30, 1998; accepted March 23, 1998 Autosomal recessive nonsyndromic sensorineural deafness segregating in a large consanguineous In- dian family was mapped to chromosome 11p14 –p15.1 defining a new locus, DFNB18. A maximum lod score of 4.4 at  0 was obtained for the polymorphic micro- satellite marker D11S1888. Haplotype analysis local- izes this gene between markers D11S1307 and D11S2368, which is approximately 1.6 cM and encom- passes the region of Usher syndrome type 1C (USH1C). We postulate that DFNB18 and USH1C are allelic vari- ants of the same gene. © 1998 Academic Press Nearly 1 in every 1000 infants is affected with clin- ically significant hearing impairment, and of these cases, approximately 75% are genetically determined (6, 8, 11). Greater than 70% of these genetically deter- mined cases are nonsyndromic and are expressed in the absence of other clinical features. Individuals with nonsyndromic sensorineural deafness inherit this dis- order as a simple Mendelian trait, with as many as 75% showing an autosomal recessive pattern of inher- itance. Of the remainder, almost 20% have autosomal dominant inheritance and 2–3% have an X-linked re- cessive pattern. In other instances, maternally inher- ited types of deafness have been directly linked to mutations within the mitochondrial genome (10). The family used for linkage analysis is from the Maharashtra state located in southwestern India. Af- fected individuals in the family demonstrated pro- found, prelingual, nonsyndromic sensorineural deaf- ness. Vestibular function and visual function were normal on clinical examination of all individuals. The presence of congenital infections was ruled out by tak- ing detailed histories from family members. After link- age to the USH1C region of chromosome 11 was con- firmed, individuals III-1 and III-6 were clinically reevaluated. In the two affected individuals, ages 18 and 19, electronystagmography (ENG) was normal with absence of nystagmus and normal caloric re- sponses. The electroretinogram (ERG) demonstrated no electrophysiological evidence of retinal involvement with normal photopic and scotopic responses. Large consanguineous families have been effectively studied to map loci responsible for recessive nonsyn- dromic hereditary hearing impairment (9). Published loci causing recessive nonsyndromic hereditary deafness were excluded by the typing of 2–9 polymorphic micro- satellite markers at regions for the known loci DFNB1- 12, B15, and B16. Pairwise and multipoint lod scores (4-point) were calculated using FASTLINK version 5.1 (2, 3), assuming a fully penetrant, recessive mutant allele and equal recombination for males and females. The ge- netic locations for recessive deafness can be found at the Hereditary Hearing Loss Home Page (http://dnalab- www.uia.ac.be/dnalab/hhh/). A genome-wide search was conducted using fluorescent markers (Linkage Mapping Set User’s Manual, P/N 904999, available from PE Ap- plied Biosystems, Foster City, CA), and linkage was ob- served with marker D11S902. Linkage was confirmed with several markers including D11S1888, which sus- tained a lod score of 4.4 – 4.5 at = 0 as the mutant allele frequency was varied from 0.01 to 0.0001. The allele frequencies of marker D11S1888 were calculated on the basis of genotyping 50 chromosomes of 25 unrelated in- dividuals from the same ethnic and geographical area. An examination of the haplotypes from affected individ- uals places the DFNB18 locus between markers 1 Present address: Laboratory of Genomic Diversity, NCI, FCRDC, Frederick, MD 21702. 2 To whom correspondence should be addressed. Telephone: (301) 402-4162. Fax: (301) 480-8019. E-mail: edwilcox@pop.nidcd.nih.gov. GENOMICS 50, 290 –292 (1998) ARTICLE NO. GE985320 290 0888-7543/98 $25.00 Copyright © 1998 by Academic Press All rights of reproduction in any form reserved.