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Identification of Autosomal Recessive Nonsyndromic Hearing Impairment Genes

Award Number: R01DC003594
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/1998
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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Identification of Autosomal Recessive Nonsyndromic Hearing Impairment Genes - PROJECT SUMMARY/ABSTRACT Hearing impairment (HI) is the most common sensory deficit in the world. Congenital HI occurs in 1-2 per 1000 newborns. Understanding the mechanism of hearing will greatly aid in the development of treatment strategies for HI. Additionally, identification of new HI genes and pathogenic variants is highly beneficial for genetic screening so that HI can be diagnosed early, and intervention can occur to maximize the child’s cognitive, social-emotional, speech and language development. The first step is to identify genes involved in the etiology of nonsyndromic (NS) HI. Although 73 genes have been identified for autosomal recessive (AR) NSHI, the vast majority of NSHI genes have yet to be uncovered. The extreme genetic heterogeneity of NSHI is due to the complex inner ear architecture. Identification of genes involved in HI is the first step in improving knowledge of the auditory process, which in turn will aid in the development of diagnostic modalities and therapeutic interventions. Annually we will ascertain ~110 ARNSHI families with at least two members affected with severe to profound bilateral sensorineural ARNSHI from Hungary (Magyar and Romani), Nigeria, and Pakistan. DNA samples from hearing-impaired family members will be screened for genes/variants that are common causes of ARNSHI within their respective population. There will be ~92 families to identify new ARNSHI genes through next-generation sequencing and data analysis that uses information on variant frequency, deleterious status, and conservation. Information clinical etiology, animal models, and inner ear expression will also be used. Candidate variants will be validated and tested for segregation with ARNSHI status within the pedigrees. Once a putative causal variant is identified we will screen our in-house collection of ARNSHI exome data, use GeneMatcher, and contact our long-term collaborators to find additional ARNSHI families that segregate potentially causal variants within the same gene. For ~20 newly identified ARNSHI genes, expression and functional studies will also be performed using zebrafish and mice models to ensure gene pathogenicity as well as to elucidate a better understanding of the role the genes play in the etiology of HI. Due to the trans-Atlantic slave trade the majority of African Americans have west African ancestry; therefore, the study of Nigerian families will impact our understanding of the etiology of HI and improve diagnostics and treatment in this minority population. Families from Pakistan and Hungary (Magyar and Romani) should yield new ARNSHI gene that also have public health importance in other populations.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2027 ( Subtotal = $0 )
2027	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	24	11/5/2026	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2026 ( Subtotal = $632,998 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	002	24	9/3/2026	SUPPLEMENT FOR EXPANSION	$10,000
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	24	9/3/2026	SUPPLEMENT FOR EXPANSION	$60,000
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	24	8/25/2026	NON-COMPETING CONTINUATION	$562,998
														Subtotal = $632,998

Issue Date FY: 2025 ( Subtotal = $1 )
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	23	3/25/2025	NON-COMPETING CONTINUATION	$1
														Subtotal = $1

Issue Date FY: 2024 ( Subtotal = $635,583 )
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	22	4/9/2024	NON-COMPETING CONTINUATION	$635,583
2024	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	002	21	6/24/2024	COMPETING CONTINUATION	$471,692
2024	2021	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	20	6/24/2024	NON-COMPETING CONTINUATION	-$471,692
														Subtotal = $635,583

Issue Date FY: 2023 ( Subtotal = $683,931 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	21	3/15/2023	COMPETING CONTINUATION	$683,931
2023	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	20	3/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $683,931

Issue Date FY: 2021 ( Subtotal = $555,990 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	20	8/17/2021	NON-COMPETING CONTINUATION	$555,990
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	002	20	8/18/2021	NON-COMPETING CONTINUATION	$0
2021	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	19	12/16/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $555,990

Issue Date FY: 2020 ( Subtotal = $555,990 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	002	19	8/28/2020	NON-COMPETING CONTINUATION	$555,990
2020	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	18	11/1/2019	NON-COMPETING CONTINUATION	$0
2020	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	17	11/1/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $555,990

Issue Date FY: 2019 ( Subtotal = $555,988 )
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	002	18	8/16/2019	NON-COMPETING CONTINUATION	$555,990
2019	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	003	16	9/19/2019	NON-COMPETING CONTINUATION	$0
2019	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	16	7/23/2019	NON-COMPETING CONTINUATION	-$306,602
2019	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Research Related to Deafness and Communication Disorders	001	17	7/23/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$306,600
														Subtotal = $555,988

Issue Date FY: 2018 ( Subtotal = $546,321 )
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	001	16	8/17/2018	NON-COMPETING CONTINUATION	$546,321
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	002	16	8/29/2018	NON-COMPETING CONTINUATION	$0
2018	2016	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	14	11/2/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $546,321

Issue Date FY: 2017 ( Subtotal = $557,173 )
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	001	15	8/21/2017	COMPETING CONTINUATION	$557,173
2017	2015	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	13	2/6/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $557,173

Issue Date FY: 2016 ( Subtotal = $332,563 )
2016	2016	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	14	9/7/2016	EXTENSION WITH OR WITHOUT FUNDS	$332,563
														Subtotal = $332,563

Issue Date FY: 2015 ( Subtotal = $329,237 )
2015	2015	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	13	6/11/2015	NON-COMPETING CONTINUATION	$329,237
														Subtotal = $329,237

Issue Date FY: 2014 ( Subtotal = $332,563 )
2014	2014	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	12	6/2/2014	NON-COMPETING CONTINUATION	$332,563
														Subtotal = $332,563

Issue Date FY: 2013 ( Subtotal = $329,921 )
2013	2013	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	11	6/26/2013	COMPETING CONTINUATION	$329,921
														Subtotal = $329,921

Issue Date FY: 2010 ( Subtotal = $0 )
2010	2008	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	10	7/14/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2009 ( Subtotal = $162,354 )
2009	2009	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Trans-NIH Recovery Act Research Support	000	10	7/15/2009	SUPPLEMENT FOR EXPANSION	$162,354
														Subtotal = $162,354

Issue Date FY: 2008 ( Subtotal = $289,460 )
2008	2008	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	10	7/9/2008	NON-COMPETING CONTINUATION	$289,460
														Subtotal = $289,460

Issue Date FY: 2007 ( Subtotal = $293,273 ) (Continued on the next page)
Grand Total All Awards = $7,725,466

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Identification of Autosomal Recessive Nonsyndromic Hearing Impairment Genes

Award Number: R01DC003594

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/1998

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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