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Staff Clinician

Medical Genetics Branch

Senior Research Physician

Medical Genetics Branch


M.D. University of New Mexico School of Medicine


Dr. Introne is a pediatrician, clinical and biochemical geneticist in the Medical Genetics Branch in NHGRI. She completed her M.D. from the University of New Mexico; pediatric residency from Children’s National Medical Center in Washington, D.C.; fellowship training in clinical genetics and clinical biochemical genetics from the NIH. Dr. Introne then worked in the Division of Pediatric Genetics at Strong Memorial Hospital in Rochester, NY, and returned to NIH as a Staff Clinician in 2004, in the Office of the Clinical Director. In 2019, she moved to the Section on Human Biochemical Genetics as a Senior Research Physician.

Scientific Summary

Dr. Introne’s research focuses on several rare inherited and metabolic disorders, including alkaptonuria, Chediak-Higashi syndrome (CHS), and Hermansky-Pudlak syndrome (HPS). For more than two decades she has been engaged in natural history studies of each of these conditions and is the Principal Investigator of the alkaptonuria, CHS, and HPS protocols.

Alkaptonuria is an inherited metabolic disorder of tyrosine degradation. The natural history study of alkaptonuria detailed the clinical manifestations and rates of progression of the disorder, and layed the foundation for clinical trials of an investigational therapeutic medication, nitisinone. Current research is focused on longitudinal evaluations to understand the progression of the disease and its phenotypic spectrum. The goal of this study is to develop a targeted therapy accessible to all patients.

Studies on CHS and HPS are translational projects with bench and clinical research components. HPS is a rare, inherited disorder with at least 11 different subtypes. While albinism and platelet dysfunction are common to all subtypes, some of the subtypes have additional complications such as pulmonary fibrosis and inflammatory bowel disease. CHS is also an ultrarare genetic disorder, with an unappreciated spectrum. While the gene for CHS, LYST, is known, little is known about the protein function. Our translational research has focused on clinical evaluation of CHS and HPS, to help delineate the natural history of the diseases, in collaboration with molecular and cellular investigations to understand the basic defects and mechanisms of disease.



Morimoto M, Nicoli ER, Kuptanon C, Roney JC, Serra-Vinardell J, Sharma P, Adams DR, Gallin JI, Holland SM, Rosenzweig SD, Barbot J, Ciccone C, Huizing M, Toro C, Gahl WA, Introne WJ, Malicdan MCV. The spectrum of LYST mutations in Chediak-Higashi syndrome: a report of novel variants and a comprehensive review of the literature. J Med Genet. (Accepted).

Kuptanon C,  Morimoto M, Nicoli ER, Stephen J, Yarnell DS, Dorward H, Owen W, Parikh S, Ozbek NY, Malbora B, Ciccone C, Gunay-Aygun M, Gahl WA, Introne WJ, Malicdan MCV. cDNA sequencing increases the molecular diagnostic yield in Chediak-Higashi syndrome. Frontiers in Genetics. 08 March 2023.

Serra-Vinardell J, Sandler MB, De Pace R, Manzella-Lapeira J, Cougnoux A, Keyvanfar K, Introne WJ, Brzostowski JA, et al. LYST deficiency impairs autophagic lysosome reformation in neurons and alters lysosome number and size. Cell. Mol. Life Sci. 2023 Jan 28;80(2):53. doi: 10.1007/s00018-023-04695-x.

Introne WJ. Nitisinone: two decades treating hereditary tyrosinaemia type 1. Lancet Diabetes Endocrinol. 2021 Jul;9(7):409-411. doi: 10.1016/S2213-8587(21)00121-2. Epub 2021 May 21.

Yarnell DS, Roney JC, Teixeira C, Freitas MI, Cipriano A, Leuschner P, Krzewski K, Stephen J, Dorward H, Gahl WA, Gochuico BR, Toro C, Malicdan MC, Introne WJ. Diagnosis of Chediak Higashi disease in a 67 year old woman. Am J Med Genet A. 2020 Dec;182(12):3007-3013.

Thimmapuram R, Bandettini WP, Shanbhag SM, Yu J, O’Brien KJ, Gahl WA, Introne WJ, Chen MY. Aortic distensibility in alkaptonuria. Mol Genet Metab. 2020 August; 130(4)289-296.

Serra-Vinardell J, Sandler MB, Pak E, Zheng W, Dutra A, Introne W, Gahl WA, et al. Generation and characterization of four Chediak-Higashi syndrome (CHS) induced pluripotent stem cell (iPSC) lines. Stem Cell Res. 2020 Jun 22;47:101883.

Sharma P, Nicoli E-R, Serra-Vinardell J, Morimoto M, Toro C, Malicdan MCV, Introne WJ. Chediak-Higashi syndrome: a review of the past, present, and future. Drug Discov Today Dis Model, 2020 Summer; 31:31-36.

Avadhanula S*, Introne WJ*, Auh S, Soldin SJ, Stolze B, Regier D, Ciccone C, Hannah-Shmouni F, Filie AC, Burman KD, Klubo-Gwiezdzinska J (*Co-First Authors). Assessment of Thyroid Function in Patients with Alkaptonuria. JAMA Netw Open. 2020 March 2; 3(3):e201357.

Shirazi N, Snow J, Ham L, Raglan GB, Wiggs EA, Summers AC, Toro C, Introne WJ. The neuropsychological phenotype of Chediak-Higashi disease. Orphanet J Rare Dis 14(1):101, 2019.

Introne WJ, Westbroek W, Groden CA, Bhambhani V, Golas GA, Baker EH, et al. Neurologic involvement in patients with atypical Chediak-Higashi disease. Neurology 88:e57-e65, 2017.

Introne WJ, Perry MB, Troendle J, Tsilou E, Kayser MA, Suwannarat P, et al. A 3-year randomized therapeutic trial of nitisinone in alkaptonuria. Mol Genet Metab 103:307-14, 2011.

MA Merideth, LB Gordon, S Clauss, V Sachdev, ACM Smith, MB Perry, CC Brewer, C Zalewski, HJ Kim, B Solomon, BP Brooks, LH Gerber, ML Turner, DL Domingo, TC Hart, J Graf, JC Reynolds, A Gropman, JA Yanovski, M Gerhard-Herman, FS Collins, EG Nabel, RO Cannon, WA Gahl, Introne WJ. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med 358:592-604, 2008. 

Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, Fitzpatrick DL, et al. Natural History of Alkaptonuria. N Engl J Med  347:2111-21, 2002.

Last updated: November 6, 2023