Arthur L. Beaudet, M.D.
Henry and Emma Meyer Chair in Molecular Genetics
Professor and Chair of Molecular and Human Genetics
Member, Institute of Medicine and National Academy of Sciences
B.S., College of the Holy Cross, 1963
M.D., Yale University School of Medicine, 1967
Resident, Pediatrics, John Hopkins Hospital, 1969
Postdoc, National Institutes of Health, 1971
National Board of Medical Examiners
American Board of Pediatrics
American Board of Medical Genetics: Clinical Biochemical Genetics, Clinical Genetics, and Clinical Molecular Genetics
Past President, American Society Human Genetics
Neuronal carnitine deficiency as a risk factor for autism; Prader-Willi and Angelman syndrome; genotype-phenotype correlations for CHRNA7; molecular diagnosis in the CLIA lab
We have described a novel inborn error of carnitine biosynthesis caused by deficiency of the X-linked TMLHE gene. This deficiency is present in 1 in 350 control males and is a risk factor for autism. This has led us to hypothesize that neuronal carnitine deficiency is a risk factor in a subset of autism patients. We suggest that abnormalities of carnitine metabolism including low dietary intake, renal loss, impaired transport, or defective synthesis may be important in up to 10-20% of autism cases, especially in males with a normal physical examination and normal MRI of the brain. Thus some cases of autism may be preventable or treatable through dietary supplementation with carnitine.
Our laboratory is studying the role of epigenetics and de novo and inherited mutations in human disease with particular emphasis on genomic imprinting and its role in Prader-Willi syndrome (PWS), Angelman syndrome (AS), and autism. Genomic imprinting is the phenomenon of differential expression of the two alleles at an autosomal locus based on their parent of origin; usually one allele is expressed and the other silenced. PWS and AS are distinct human disorders characterized by neurobehavioral abnormalities and intellectual disability. They are caused by deficiency of paternally (PWS) or maternally (AS) expressed genes within chromosome 15q11-q13. Our laboratory has contributed to identification of molecular defects causing PWS and AS, identified the UBE3A locus encoding E6-AP ubiquitin-protein ligase as the AS gene, and made numerous mouse models related to PWS and AS. We are currently exploring the use of oligonucleotides in mice to knockdown the antisense transcript for UBE3A to unsilence expression of the sense transcript from the paternal chromosome as a treatment for Angelman syndrome.
The lab is also focused on the clinical implementation of new molecular methods for genetic diagnosis including the use of chromosomal microarray analysis (CMA), whole exome and whole genome sequencing, and cell-based noninvasive prenatal diagnosis. We have a special focus on analysis of deletions of chromosome 15q13.3 that can cause intellectual disability, autism, schizophrenia, epilepsy, and aggressive behavior. This has led to detailed genotyping for the CHRNA7 gene which maps to 15q13.3 and encodes a neuronal nicotinic acetylcholine receptor, which we believe is important in genetic causes of neurobehavioral disorders.
- Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM (2013). Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders. N. Engl. J. Med. [Epub ahead of print] PubMed PMID: 24088041
- Schaaf CP, Gonzalez-Garay ML, Xia F, Potocki L, Gripp KW, Zhang B, Peters BA, McElwain MA, Drmanac R, Beaudet AL, Caskey CT, Yang Y. Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism. Nat. Genet., in press.
- Beaudet AL (2013). The utility of chromosomal microarray analysis in developmental and behavioral pediatrics. Child. Dev. 84(1): 121-32. PubMed PMID: 23311723
- Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L (2012). Chromosomal microarray versus karyotyping for prenatal diagnosis. N. Engl. J. Med. 367(23): 2175-84. PubMed PMID: 23215555
- Meng L, Person RE, Beaudet AL (2012). Ube3a-ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a. Hum. Mol. Genet. 21(13): 3001-12. PubMed PMID: 22493002
- Bi W, Breman A, Shaw CA, Stankiewicz P, Gambin T, Lu X, Cheung SW, Jackson LG, Lupski JR, Van den Veyver IB, Beaudet AL (2012). Detection of ≥1Mb microdeletions and microduplications in a single cell using custom oligonucleotide arrays. Prenat. Diagn. 32(1): 10-20. PubMed PMID: 22470934
- Beaudet AL (2012). Neuroscience. Preventable Forms of Autism? Science 338(6105): 342-343. PubMed PMID: 23087240
Awards and Honors
2011: Elected to National Academy of Sciences
2007: Appointed, NIH Gene Therapy Resource Program Scientific Review Board
2007: Recipient, The American Society of Human Genetics Allen Award, October 2007
2002: Colonel Harland Sanders Award for Lifetime Achievement in Genetic Research and Education, March of Dimes
2001: The Dr. Claudia Benton Award for Scientific Research, Angelman Syndrome Foundation
2001: Baylor Medical Alumni Association Distinguished Faculty Award, 2001
1999: Michael E. DeBakey Excellence in Research Award
1999: Texas Genetics Society Barbara H. Bowman Award
1996-present: Henry and Emma Meyer Professor
Arthur L. Beaudet, M.D.
Henry and Emma Meyer Professor and Chair
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.