Henry and Emma Meyer Chair and Professor, Molecular and Human Genetics
Professor, Molecular and Cell Biology
Professor, Department of Pediatrics
Program in Integrative Molecular and Biomedical Sciences
Baylor College of Medicine

Texas Children's Hospital
One Baylor Plaza, Rm T619
Houston, TX 77030

http://www.nasonline.org/member-directory/members/3000420.html

Biosketch:

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.

Our lab has studied 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.

Declared conflicts of interest on file (10/07/2019)

Selected Bibliography: