Heidi L. Rehm, Ph.D. Associate Molecular Geneticist Instructor in Pathology (BWH) Director, Clinical Molecular Genetics Training Program (ABMG/HMS) Associate Director, HMS Center for Hereditary Deafness HPCGG 65 Landsdowne St. Cambridge, MA 02139 Tel: (617) 768-8291 Email: hrehm@hms.harvard.edu
I am a molecular geneticist and maintain activities in clinical diagnostics, education and research. My clinical role involves daily signout of hearing loss and cardiovascular disease testing for the Laboratory for Molecular Medicine in addition to an administrative role in overseeing the laboratory. My educational activities include directing the Clinical Molecular Genetics Training Program at Harvard Medical School and educating both the student, professional and lay communities on topics including basic genetics, genetic hearing loss, and molecular diagnostics. In addition, I am Associate Director of the Harvard Medical School Center for Hereditary Deafness (http://hearing.harvard.edu), overseeing many activities related to this Center. The main areas of my research include studies of: 1) Norrie disease; 2) genotype/phenotype studies in hereditary hearing loss; 3) access to and quality of genetics services for hereditary hearing loss; and 4) the development of molecular diagnostic tools for identifying genetic causes of hearing loss. Norrie disease My early research on Norrie disease began when I mapped a family with deafness, blindness and vascular disease to the Norrie disease locus and showed for the first time that this disease involves the vascular system. Since then, my recent work has involved the characterization of the hearing loss phenotype in both mice and humans in order to investigate the biological role of the NDP gene and its protein, norrin, and the mechanism of pathogenesis in Norrie disease. One of the challenges in this field is the paucity of clinical data that defines the phenotypic spectrum of this disease, particularly with respect to patients with defined mutations in the NDP gene. As such, we have focused our recent efforts on characterizing the natural clinical history of Norrie disease in patients with identified NDP mutations. To date we have recruited and collected detailed clinical information on 56 patients. Through this research we are gaining a better understanding of the visual, audiological, cognitive and vascular deficits in these patients. Related publications: Rehm HL, Gutiérrez-Espeleta GA, Garcia R, Jiménez G, Khetarpal U, Priest JM, Sims KB, Keats      BJB, and Morton CC. Norrie disease gene mutation in a large Costa Rican kindred with a novel      phenotype including peripheral vascular disease. Hum Mutat 1997;9:402-408. Rehm HL, Zhang DS, Brown MC, Burgess B, Halpin C, Berger W, Morton CC, Corey DP, and      Chen ZY. Vascular defects and sensorineural hearing loss in a mouse model of Norrie disease.      J Neurosci 2002;22:4286. Halpin C, Owen G, Guti??rrez-Espeleta GA, Sims KB, Rehm HL. Audiological features of Norrie      disease. Ann Otol Rhinol Laryngol 2005;114:533-8. Genotype-phenotype studies in hereditary hearing loss The main focus of these studies has been to examine the clinical phenotype and mutation spectrum in patients with hearing loss due to connexin 26 (Cx26) mutations. Through these efforts we have identified novel mutations and defined certain mutations with milder phenotypes. In addition, we have recently submitted a paper on additional clinical findings observed in patients with Cx2626 mutations and the implications for Cx26 gene testing. Related publications: Kenna MA, Wu B-L, Cotanche DA, Korf BR, and Rehm HL. Connexin 26 studies in patients with      sensorineural hearing loss. Arch Otolaryngol Head Neck Surg 2001;127:1037-1042. Snoeckx RL, et al. GJB2 mutations and degree of hearing loss: a multicenter study. Am J Hum      Genet. 2005; 77(6):945-57. Kenna MA, Rehm HL, Robson C, Frangulov A, McCallum J, Yaeger D, Krantz ID. Additional      Clinical Manifestations in Children with Sensorineural Hearing Loss and Biallelic GJB2      Mutations: Who Should Be Offered GJB2 Testing? Am J Med Genet. Submitted. Putcha GV et al. A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations      in a large North American cohort. Submitted. Access to and quality of genetics services for hereditary hearing loss Through a survey mechanism we have been evaluating the quality of genetic services for hearing loss. We have identified weaknesses in this area of medicine and have developed recommendations for how to improve some of these services. One outcome is the incorporation of genetic counseling directly into the Otolaryngology service to provide patients and families easier access to genetic knowledge and services. The development of molecular diagnostic tools for identifying genetic causes of hearing loss In the past 2 years we have focused on the development and validation of the Affymetrix resequencing technology for identification of genetic causes of hearing loss. Through these studies we have determined the analytical performance characteristics of this platform as well as identified novel variants in seven different hearing loss genes. Other publications: Cluss RG, Saxena AS, Rehm HL, Schoenecker JG, and Boothby JT. Coordinate synthesis and      turnover of heat shock proteins in Borrelia burgdorferi: Degradation of DnaK during recovery from      heat shock. Infect Immun 1996;64:1736-43. Eudy, JD, Weston MD, Yao S, Hoover DM, Rehm HL, Ma-Edmonds M, Yan D, Ahmad I, Cheng      JJ, Ayuso C, Cremers C, Davenport S, Moller C, Talmadge CB, Beisel KW, Tamayo M, Morton      CC, Swaroop A, Kimberling WJ, and Sumegi J. Mutation of a gene encoding a protein with      extracellular matrix motifs in Usher syndrome type IIa. Science 1998;280:1753-1757. Rehm HL and Morton CC. A new age in the genetics of deafness. Genet Med 1999;1:295-302. Rehm HL. The genetics of deafness and connexin 26 testing. Volta Voices 2000;7:10-16. Pfister MHF and Rehm HL. Glossary for hereditary hearing impairment. Ear Hear 2003;260-265. Rehm HL. Genetics and the genome project. Ear Hear 2003;270-274. Corey DP, Garcia-Anoveros J, Holt JR, Kwan KY, Lin S-Y, Vollrath MA, Amalfitano A, Cheung      ELM, Derfler BH, Duggan A, Geleoc GSG, Gray PA, Hoffman MP, Rehm HL, Tamasauskas D,      Zhang D-S. TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate      hair cells. Nature 2004;432:723-30. Roberts A, Rehm HL, McDonough B, Barr S, Seidman CE, Seidman J, and Kucherlapati R. The      PTPN11 gene is not implicated in nonsyndromic familial hypertrophic cardiomyopathy. Amer J      Hum Genet 2005;132:333-4. Rehm HL. Clinical Molecular Genetics: Moleculars diagnostics for hearing loss. Chapter in Current      Protocols in Human Genetics. 2005. Rehm HL. A genetic approach to the child with sensorineural hearing loss. Seminars in      Perinatology 2005;29:173-181