Associate Professor, Department of Molecular and Human Genetics
Module Chair, Medical Student Curriculum in Genetics
Director, Ben Taub Genetics Clinic

B.A., Boston University, 1983
M.D., Boston University School of Medicine, 1987
Resident in Pathology, University of Massachusetts, 1993
Fellow in Fetal and Perinatal Pathology, Brown University, 1994
Fellow in Medical Genetics, Baylor College of Medicine, 1996

RESEARCH INTERESTS:

My primary interest involves the diagnosis, counseling, and management of individuals with developmental and genetic disorders. I direct the medical student curriculum in Genetics, and serve on curriculum committees at the School of Medicine and School of Allied Health Sciences. My research involves the multi-disciplinary clinical study and characterization of Smith-Magenis syndrome (SMS), duplication 17p11.2 syndrome (Potocki-Lupski syndrome, PTLS), duplication 7q11.23 syndrome, and the Potocki-Shaffer syndrome (PSS).

SMS is associated with a heterozygous deletion within 17p11.2 or point mutation of RAI1 that maps within 17p11.2. While the phenotype is variable among patients with the same sized deletion, all patients have cognitive impairment, neurobehavioral abnormalities, and sleep disturbances including an inversion of the circadian rhythm of melatonin. Clinical evaluations have been completed through the General Clinical Research Center (GCRC) at the Texas Children's Hospital (TCH). Evaluation of individuals with point mutations of RAI1 will help determine genotype-phenotype correlation.

Duplication 17p11.2 represents the reciprocal recombination of the common SMS deletion. The clinical phenotype of persons with dup17p11.2 is distinct from that of SMS and consists of infantile hypotonia and failure to thrive, mildly dysmorphic facial features, cognitive impairment, and autistic features. Although sleep disturbances are not recognized clinically, patients evaluated in the GCRC were found to have sleep disordered breathing such as central and obstructive sleep apnea. Cardiovascular anomalies are seen in approximately 50 percent of patients. Persons with duplication 17p11.2 are being recruited for clinical evaluations in the GCRC, and for molecular analyses. Clinical comparisons of PTLS and SMS, in conjunction with molecular analyses, will provide insight as to dosage sensitivity and the roles of the genes within this region.

Another microduplication syndrome is one caused by the duplication of 7q11.23. Microdeletion of this region is causes the Williams-Beuren syndrome (WBS). In general, persons with WBS have very good expressive language and are talkative and outgoing. In contrast, persons with duplication 7q11.23 have severe deficits in expressive language and autistic features. A GCRC protocol has been established to evaluate patients with dup(7)(q11.23q11.23). Clinical comparisons in conjunction with molecular analyses, will provide insight as to dosage sensitivity and the roles of the genes within this region.

PSS is a contiguous gene deletion syndrome due to an interstitial deletion within the short arm of chromosome 11 [ del(11)(p11.2p12)]. Clinical findings of PSS include mental retardation, multiple exostoses, biparietal foramina, and genital anomalies in males. The presence of multiple exostoses is associated with deletion of EXT2 and the presence of biparietal foramina is associated with the deletion of ALX4. Specific genes related to mental retardation or other abnormalities have yet to be identified. Individuals with duplication of this region have also been identified.

SELECTED PUBLICATIONS:

1. Potocki L, Bi W, Treadwell-Deering D, Carvalho CM, Eifert A, Friedman EM, Glaze D, Krull K, Lee JA, Lewis RA, Mendoza-Londono R, Robbins-Furman P, Shaw C, Shi X, Weissenberger G, Withers M, Yatsenko SA, Zackai EH, Stankiewicz P, Lupski JR (2007). Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Am. J. Hum. Genet. 80: 633-649.

2. Bi W, Saifi GM, Girirajan S, Shi X, Szomju B, Firth H, Magenis RE, Potocki L, Elsea SH, Lupski JR (2006). RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion Smith-Magenis syndrome. Am. J. Med. Genet. A. 140: 2454-2463.

3. Madduri N, Peters SU, Voight RG, Llorent AM, Lupski JR, Potocki L (2006). Cognitive and adaptive behavior profiles in Smith-Magenis syndrome. J. Dev. Behav. Pediatr. 27: 188-192.

4. Goldman AM, Potocki L, Walz K, Lynch JK, Glaze DG, Lupski JR, Noebels JL (2006). Epilepsy and Chromosomal Rearrangements in Smith-Magenis Syndrome [del(17)(p11.2p11.2)]. J. Child Neurol. 21: 93-98.

5. Yatsenko SA, Treadwell-Deering D, Krull K, Lewis RA, Glaze D, Stankiewicz P, Lupski JR, Potocki L (2005). Trisomy 17p10-p12 due to mosaic supernumerary marker chromosome: Delineation of molecular breakpoints and clinical phenotype, and comparison to other proximal 17p segmental duplications. Am. J. Med. Genet. A. 138: 175-180.

6. Wakui K, Gregato G, Ballif BC, Glotzbach CD, Bailey KA, Kuo PL, Sue WC, Sheffield LJ, Irons M, Gomez EG, Hecht JT, Potocki L, Shaffer LG (2005). Construction of a natural panel of 11p11.2 deletions and further delineation of the critical region involved in Potocki-Shaffer syndrome. Eur. J. Hum. Genet. 13: 528-540.

7. Potocki L, Shaw CJ, Stankiewicz P, Lupski JR (2003). Variability in clinical phenotype despite common chromosomal deletion in Smith-Magenis syndrome [del(17)(p11.2p11.2)]. Genet. Med. 5: 430-434.

8. Potocki L, Glaze D, Tan DX, Park SS, Kashork CD, Shaffer LG, Reiter R, Lupski JR (2000). Circadian rhythm abnormalities of melatonin in Smith-Magenis syndrome. J. Med. Genet. 37: 428-433.

9. Potocki L, Chen KS, Park SS, Osterholm DE, Withers MA, Kimonis V, Summers AM, Meschino WS, Anyane-Yeboa K, Kashork CD, Shaffer LG, Lupski JR (2000). Molecular mechanism for dup17p11.2-the homologous recombination reciprocal of the Smith-Magenis microdeletion. Nat. Genet. 24: 84-87.

For more publications, see listing on Pub Med.

CLINICAL INFORMATION:

Board Certifications:
National Board of Medical Examiners
American Board of Medical Genetics, Clinical Genetics
American Board of Pathology, Clinical Pathology

Primary Focus:
Developmental disorders, Congenital anomalies

Professional Organizations:
Member, American Society of Clinical Pathologists
Member, College of American Pathologists
Member, American Society of Human Genetics
Fellow, American College of Medical Genetics
Professional Advisory Board Member, Multiple Hereditary Exostoses Coalition
Professional Advisory Board Member, Parent and Researchers Interested in Smith-Magenis Syndrome (PRISMS) Professional Advisory Board

CONTACT INFORMATION:

Lorraine Potocki, M.D., F.A.C.M.G.
Texas Children's Hospital
Clinical Care Center
6701 Fannin, CC1560
Houston, Texas 77030, U.S.A.
Mail Stop: CC1560

Phone: 832-822-4292
Fax: 832-825-4294
E-mail:

dup 17p11.2 GCRC protocol: http://www.bcm.edu/genetics/dup17p11.2/

dup 7q11.23 GCRC protocol: http://www.bcm.edu/genetics/dup7q11.23/

TCH LINK: http://www.texaschildrenshospital.org/findadoctor/displaybio.asp?person_id=498

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