Email

abeaudet@bcm.edu

Positions

Henry and Emma Meyer Chair and Professor

Molecular and Human Genetics
Baylor College of Medicine
Houston, TX US

Professor

Molecular & Cellular Biology
Baylor College of Medicine
Houston, Texas United States

Professor

Pediatrics
Baylor College of Medicine
Houston, Texas United States

Faculty Member

Program in Integrative Molecular and Biomedical Sciences
Baylor College of Medicine
Houston, Texas United States

Education

BS from College Of The Holy Cross

01/1963 - Worcester, MA United States

MD from Yale University School Of Medicine

01/1967 - New Haven, CT United States

Residency at Johns Hopkins Hospital

01/1969 - Baltimore, MD United States

Post-Doctoral Fellowship at National Institutes of Health

01/1971 - Bethesda, Maryland United States

Certifications

Clinical Molecular Genetics

American Board of Medical Genetics

Diplomate

National Board of Medical Examiners

General Pediatrics

American Board of Pediatrics

Clinical Biochemical Genetics

American Board of Medical Genetics

Clinical Genetics

American Board of Medical Genetics

Honors & Awards

Victor A. McKusick Leadership Award

Recipient, October 2017

American Society of Human Genetics

National Academy of Sciences

Elected, 2011

NIH Gene Therapy Resource Program Scientific Review Board

Appointed, 2007

The American Society of Human Genetics Allen Award

Recipient, October 2007

Colonel Harland Sanders Award for Lifetime Achievement in Genetic Research and Education

2002, March of Dimes

The Dr. Claudia Benton Award for Scientific Research

2001, Angelman Syndrome Foundation

Baylor Medical Alumni Association Distinguished Faculty Award

2001

Michael E. DeBakey Excellence in Research Award

1999

Texas Genetics Society Barbara H. Bowman Award

1999

Henry and Emma Meyer Chair in Molecular Genetics

1996-present

Professional Interests

• 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

Professional Statement

In 2012, we 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 brain carnitine deficiency can cause autism in a subset of 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. We suggest that a strong male predominance is explained by lack of X-inactivation of SLC6A14, an X-linked carnitine transporter that transports carnitine across the blood-brain barrier (BBB). Wild-type female mice transport radioactive carnitine across the BBB better than males and mice null for Slc6a14 have impaired transport. This hypothesis has now been described in depth in BioEssays.
Our lab has studies the role of genomic imprinting and its effect in Prader-Willi syndrome (PWS), Angelman syndrome (AS), and autism. They are caused by deficiency of paternally (PWS) or maternally (AS) expressed genes within chromosome 15q11-q13. We have 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 have recently demonstrated 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. We are collaborating with Ionis Pharmaceuticals to develop a phase 1 trial of oligonucleotide treatment for AS. We are preparing a “humanized” mouse expressing the human UBE3A antisense for use in preclinical studies.
We are developing a new form of genetic prenatal diagnosis isolating fetal cells from the maternal blood that we believe would be a major improvement over existing tests. We have published evidence for the feasibility of fetal trophoblastic cell-based noninvasive prenatal testing as listed.
Together with Mary Dickinson, we lead the Baylor component of an international collaboration to analyze the function of all mouse genes called the KnockOut Mouse Project (KOMP). A large NIH grant received a renewal with five years of funding. A recent KOMP publication is listed.

Websites

Selected Publications

• Beaudet AL "Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias: A hypothesis." Bioessays. 2017 Aug;39(8) Pubmed PMID: 28703319
• Kølvraa S, Singh R, Normand EA, Qdaisat S, van den Veyver IB, Jackson L, Hatt L, Schelde P, Uldbjerg N, Vestergaard EM, Zhao L, Chen R, Shaw CA, Breman AM, Beaudet AL "Genome-wide copy number analysis on DNA from fetal cells isolated from the blood of pregnant women." Prenat Diagn. 2016 Dec;36(12):1127-1134. Pubmed PMID: 27761919
• Dickinson ME, Flenniken AM, Ji X, Teboul L, Wong MD, (...), Beaudet AL, Bućan M, Murray SA "High-throughput discovery of novel developmental phenotypes.." Nature. 2016 Sep 14;537:508-514. Pubmed PMID: 27626380
• Breman AM, Chow JC, U'Ren L, Normand EA, Qdaisat S, Zhao L, Henke DM, Chen R, Shaw CA, Jackson L, Yang Y, Vossaert L, Needham RH, Chang EJ, Campton D, Werbin JL, Seubert RC, Van den Veyver IB, Stilwell JL, Kaldjian EP, Beaudet AL "Evidence for feasibility of fetal trophoblastic cell-based noninvasive prenatal testing.." Prenat. Diagn.. 2016 Sep 12;36:1-11. Pubmed PMID: 27616633

Memberships

American Society of Human Genetics

Past President