Assistant Professor, Department of Molecular and Human Genetics

B.S., Brigham Young University, 1993
M.D./Ph.D., University of Iowa, 2000
Pediatrics Residency, University of Utah, 2003
Clinical Genetics Residency, Baylor College of Medicine, 2005

RESEARCH INTERESTS:

In our laboratory we are working to identify and characterize the genes that cause common birth defects. Congenital diaphragmatic hernia (CDH) affects about 1 in every 2,500 newborns. In most children with CDH, an abnormal opening in the diaphragm allows abdominal organs, like the liver and intestines, to enter into the chest during fetal life. This invasion often interferes with normal lung development causing severe respiratory problems at birth. Children with CDH typically require surgical intervention followed by prolonged hospitalizations. Even with optimal care, mortality ranges between 40-60 percent. By understanding the genes that cause CDH, we hope to find ways of preventing CDH and improving patient outcomes. We are using novel molecular cytogenetic techniques to identify regions of the genome that are likely to harbor CDH-related genes. To date, over 20 such regions have been identified and several have been shown to contain genes that are critical for normal diaphragm development. We are also developing mouse models of CDH that will help us understand the molecular mechanisms though which these genes function and how these genes interact with each other during development.

Esophageal atresia/tracheoesophageal fistula (EA/TEF) is another life-threatening birth defect that has become a focus of interest in our laboratory. During development the esophagus (stomach tube) and the trachea (windpipe) develop from a common progenitor called the anterior foregut tube. In about 1 in 3,500 newborns, the development of these tubes is abnormal resulting in failure of the esophagus to reach the stomach (esophageal atresia) or an abnormal connection between the trachea and esophagus (tracheoesophageal fistula). Approximately 50 percent of EA/TEF cases occur in association with additional anomalies and 10 percent of cases have a constellation of findings that in known as VACTERL association (Vertebral, Anal, Cardiac, Tracheoesophageal Fistula, Renal, Limb). Since EA/TEF is also sporadic birth defect we are using the same approach we have taken for CDH to identify EA/TEF-related genes.

Many of the candidate genes for CDH and EA/TEF are transcription factors that play key roles in early development. The Atrophin 2 gene on chromosome 1p encodes two proteins that work with a specific set of transcription factors to alter gene expression. It is likely that Atrophin 2 plays an important role in patients with 1p36 deletion syndrome which affects 1 in ever 5000 newborns. We are presently using an allelic series of Atrophin 2 mutant mice to study the role of this gene in heart, brain, kidney and inner ear development.

SELECTED PUBLICATIONS:

1. Holder AM, Klaassens M, Tibboel D, de Klein A, Lee B, Scott DA (2007). Genetic factors in congenital diaphragmatic hernia. Am. J. Hum. Genet. 80: 825-845.

2. Scott DA, Klaassens M, Holder AM, Lally KP, Fernandes CJ, Galjaard RJ, Tibboel D, de Klein A, Lee B (2007). Genome-wide oligonucleotide-based array comparative genome hybridization analysis of non-isolated congenital diaphragmatic hernia. Hum. Mol. Genet. 16: 424-430.

3. Scott DA (2007). Genetics of congenital diaphragmatic hernia. Semin. Pediatr. Surg. 16: 88-93.

4. Klaassens M, Galjaard RJ, Scott DA, Brüggenwirth HT, van Opstal D, Fox MV, Higgins RR, Cohen-Overbeek TE, Schoonderwaldt EM, Lee B, Tibboel D, de Klein A (2007). Prenatal detection and outcome of congenital diaphragmatic hernia (CDH) associated with deletion of chromosome 15q26: two patients and review of the literature. Am. J. Med. Genet. A. 143: 2204-2212

5. Cheung SW, Shaw CA, Scott DA, Patel A, Sahoo T, Bacino CA, Pursley A, Li J, Erickson R, Gropman AL, Miller DT, Seashore MR, Summers AM, Stankiewicz P, Chinault AC, Lupski JR, Beaudet AL, Sutton VR (2007). Microarray-based CGH detects chromosomal mosaicism not revealed by conventional cytogenetics. Am. J. Med. Genet. A. 143:1679-1686

6. Li C, Scott DA, Hatch E, Tian X, Mansour SL (2007). Dusp6 (Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development. Development 134: 167-176

7. Schlaubitz S, Yatsenko SA, Smith LD, Keller KL, Vissers LE, Scott DA, Cai WW, Reardon W, Abdul-Rahman OA, Lammer EJ, Lifchez CA, Magenis E, Veltman JA, Stankiewicz P, Zabel BU, Lee B (2007). Ovotestes and XY sex reversal in a female with an interstitial 9q33.3-q34.1 deletion encompassing NR5A1 and LMX1B causing features of Genitopatellar syndrome. Am. J. Med. Genet. A. 143: 1071-1081

8. Klaassens M, Scott DA, van Dooren M, Hochstenbach R, Eussen HJ, Cai WW, Galjaard RJ, Wouters C, Poot M, Laudy J, Lee B, Tibboel D, de Klein A (2006). Congenital diaphragmatic hernia associated with duplication of 11q23-qter. Am. J. Med. Genet. A. 140: 1580-1586

9. Scott DA, Cooper ML, Stankiewicz P, Patel A, Potocki L, Cheung SW (2005). Congenital diaphragmatic hernia in WAGR syndrome. Am. J. Med. Genet. A. 134: 430-433.

For more publications, see listing on Pub Med.

CLINICAL INFORMATION:

Board Certifications:
National Board of Pediatrics
American Board of Medical Genetics

Professional Organizations:
Member, American Society of Human Genetics
Member, American Academy of Pediatrics

CONTACT INFORMATION:

Daryl Scott, M.D., Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, R813
Houston, Texas 77030, U.S.A.
Mail Stop: BCM225

Phone: 713-798-2013
Fax:
E-mail:

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