Published online September 1, 2006
PEDIATRICS Vol. 118 No. 3 September 2006, pp. 985-994 (doi:10.1542/peds.2005-2519)
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ARTICLE

Simultaneous Multigene Mutation Detection in Patients With Sensorineural Hearing Loss Through a Novel Diagnostic Microarray: A New Approach for Newborn Screening Follow-up

Phyllis Gardner, MDa, Eneli Oitmaab, Anna Messner, MDc, Lies Hoefsloot, PhDd, Andres Metspalu, MD, PhDe,f and Iris Schrijver, MDg

a Departments of Medicine
c Otolaryngology/Head and Neck Surgery and Pediatrics
g Pathology, Stanford University School of Medicine, Stanford, California
b Asper Biotech, Ltd, Tartu, Estonia
d Department of Human Genetics, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands
e Institute of Molecular and Cell Biology, University of Tartu/Estonian Biocentre, Tartu, Estonia
f MDC, UL, Tartu University Hospital, Tartu, Estonia

OBJECTIVE. The advent of universal newborn hearing screening in the United States and other countries, together with the identification of genes involved in the process of hearing, have led to an increase in both the need and opportunity for accurate molecular diagnosis of patients with hearing loss. Deafness and hearing impairment have a genetic cause in at least half the cases. The molecular genetic basis for the majority of these patients remains obscure, however, because of the absence of associated clinical features in ~70% (ie, nonsyndromic hearing loss) of patients, genetic heterogeneity, and the lack of molecular genetic tests that can evaluate a large number of mutations across multiple genes.

DESIGN. We report on the development of a diagnostic panel with 198 mutations underlying sensorineural (mostly nonsyndromic) hearing loss. This panel, developed on a microarray, is capable of simultaneous evaluation of multiple mutations in 8 genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5 and the mitochondrial genes encoding 12S rRNA and tRNA-Ser[UCN]).

RESULTS. The arrayed primer extension array for sensorineural hearing loss is based on a versatile platform technology and is a robust, cost-effective, and easily modifiable assay. Because hearing loss is a major public health concern and common at all ages, this test is suitable for follow-up after newborn hearing screening and for the detection of a genetic etiology in older children and adults.

CONCLUSIONS. Comprehensive and relatively inexpensive genetic testing for sensorineural hearing loss will improve medical management for affected individuals and genetic counseling for their families.

Key Words: APEX • sensorineural hearing loss • newborn hearing screening • connexin • microarray • molecular diagnostic

Abbreviations: SNHL—sensorineural hearing loss • OMIM— Online Mendelian Inheritance in Man • APEX—arrayed primer extension • gDNA—genomic deoxyribonucleic acid • PCR—polymerase chain reaction

Accepted Apr 11, 2006.


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