Stowers Institute researchers Karen Staehling-Hampton, Ph.D., Managing Director of Molecular Biology, and Olivier Pourquié, Ph.D., Investigator, collaborated with colleagues from around the world to show that genes known to cause spinal mutations in chick and mouse model systems also play an important role in human patients with congenital vertebral abnormalities.
Working with samples from 31 patients at Boston Children's Hospital with various congenital vertebral defects, the team sequenced five genes thought to be involved in the malformations. In a patient of Puerto Rican descent, the team discovered a mutation in the MESP2 gene -- a mutation that completely disrupted the function of the gene.
The affected patient had Spondylothoracic Dysostosis, also known as Jarcho-Levin Syndrome. Spondylothoracic Dysostosis is a rare genetic disorder characterized by distinctive malformations of the vertebrae and ribs, respiratory problems, and other abnormalities. Infants born with Spondylothoracic Dysostosis have short necks, limited neck motion, and are short in stature. Spondylothoracic Dysostosis is prevalent in the Puerto Rican population.
Sequencing of samples from additional Spondylothoracic Dysostosis patients of Puerto Rican descent demonstrated the same mutation in the MESP2 gene.
"Spondylothoracic Dysostosis was first characterized in the Puerto Rican population 70 years ago," said Dr. Staehling-Hampton, co-equal first author on the paper, "but the gene mutation causing the condition was not isolated until now. The MESP2 mutation can be detected by a simple assay, so identification of this mutation will allow people who have a family history of Spondylothoracic Dysostosis to determine if they carry the mutation and whether they are at risk of passing the disorder on to future generations."
"After working for many years to study spinal formation in chicks and mice, it is rewarding to expand our investigation to clinical applications," said Dr. Pourquié, senior author on the publication. "We will continue to work with colleagues to collect more samples from patients with congenital vertebral abnormalities and sequence more genes to look for causative mutations. Additionally, we will sequence MESP2 in a larger collection of DNA samples from Puerto Rico to determine the carrier frequency of this MESP2 mutation in the general Puerto Rican population."
The discovery was published May 15 on the Web site of the American Journal of Human Genetics.
Kym Delventhal, a Laboratory Manager in the Stowers Institute's Molecular Biology Facility, also contributed to this publication.
Additional contributing authors include Alberto Cornier, Department of Molecular Medicine, La Concepción Hospital, San German, Puerto Rico and Department of Biochemistry, Ponce School of Medicine, Ponce, Puerto Rico; Yumiko Saga, Division of Mammalian Development, National Institute of Genetics, Mishima, Japan; Jean-Francois Caubet, Department of Orthopaedic Surgery, Children's Hospital Boston; Nobuo Sasaki, Division of Mammalian Development, National Institute of Genetics, Mishima, Japan; Sian Ellard, Department of Molecular Genetics, Royal Devon and Exeter Hospital, Exeter, United Kingdom; Elizabeth Young, Department of Molecular Genetics, Royal Devon and Exeter Hospital, Exeter, United Kingdom; Norman Ramirez, Department of Orthopaedics, La Concepción Hospital, San German, Puerto Rico; Simon Carlo, Department of Molecular Medicine, La Concepción Hospital, San German, Puerto Rico and Department of Genetics, San Juan Bautista School of Medicine, Caguas, Puerto Rico; Jose Torres, Department of Biochemistry, Ponce School of Medicine, Ponce, Puerto Rico; John Emans, Department of Orthopaedic Surgery, Children's Hospital Boston; and Peter Turnpenny, Clinical Genetics Department, Royal Devon and Exeter Hospital, Exeter, United Kingdom.
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