candidate's description): The Smith-Magenis syndrome (SMS) is a multiple anomaly, mental retardation syndrome associated with a deletion of chromosome 17 band p11.2. Characteristic features include short stature, dysmorphic facial appearance, brachydactyly, behavioral problems, and sleep disturbances. SMS individuals can also be affected with ophthalmic, otolaryngologic, cardiac and renal anomalies. Although SMS is considered to be a contiguous gene deletion syndrome caused by haploinsufficiency of many physically contiguous but functionally unrelated loci, the molecular etiology remains unknown. There is phenotypic variation among SMS individuals suggesting the presence of recessive alleles or modifier loci within this region. Currently, only a few genes have been mapped to the SMS region and their contribution to this complex phenotype remains speculative. The candidate proposes to isolate and characterize genes within the SMS critical region, and elucidate any genotype/phenotype correlation in SMS. She also proposes to further characterize the genomic structure and mechanism of deletion of this region. SMS patients are followed at the Texas Children's Hospital Genetic Clinic and others are referred for consultation and clinical research through the General Clinical Research Center for Children (GCRC) by colleagues across the country. Cell lines are established on 86 SMS patients, and a YAC contig spanning the SMS region is being developed.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD001149-05
Application #
6182067
Study Section
Mental Retardation Research Committee (HDMR)
Program Officer
Oster-Granite, Mary Lou
Project Start
1996-08-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2002-07-31
Support Year
5
Fiscal Year
2000
Total Cost
$84,927
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Soler-Alfonso, Claudia; Motil, Kathleen J; Turk, Catherine L et al. (2011) Potocki-Lupski syndrome: a microduplication syndrome associated with oropharyngeal dysphagia and failure to thrive. J Pediatr 158:655-659.e2
Boone, Philip M; Reiter, Russel J; Glaze, Daniel G et al. (2011) Abnormal circadian rhythm of melatonin in Smith-Magenis syndrome patients with RAI1 point mutations. Am J Med Genet A 155A:2024-7
Sanchez-Valle, Amarilis; Pierpont, Mary Ella; Potocki, Lorraine (2011) The severe end of the spectrum: Hypoplastic left heart in Potocki-Lupski syndrome. Am J Med Genet A 155A:363-6
Potocki, Lorraine; Bi, Weimin; Treadwell-Deering, Diane et al. (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 80:633-49
Goldman, Alica M; Potocki, Lorraine; Walz, Katherina et al. (2006) Epilepsy and chromosomal rearrangements in Smith-Magenis Syndrome [del(17)(p11.2p11.2)]. J Child Neurol 21:93-8
Madduri, Niru; Peters, Sarika U; Voigt, Robert G et al. (2006) Cognitive and adaptive behavior profiles in Smith-Magenis syndrome. J Dev Behav Pediatr 27:188-92
Bi, Weimin; Saifi, G Mustafa; Shaw, Christine J et al. (2004) Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith-Magenis syndrome. Hum Genet 115:515-24
Potocki, Lorraine; Shaw, Christine J; Stankiewicz, Pawel et al. (2003) Variability in clinical phenotype despite common chromosomal deletion in Smith-Magenis syndrome [del(17)(p11.2p11.2)]. Genet Med 5:430-4
Smith, Ann C M; Gropman, Andrea L; Bailey-Wilson, Joan E et al. (2002) Hypercholesterolemia in children with Smith-Magenis syndrome: del (17) (p11.2p11.2). Genet Med 4:118-25
Liburd, N; Ghosh, M; Riazuddin, S et al. (2001) Novel mutations of MYO15A associated with profound deafness in consanguineous families and moderately severe hearing loss in a patient with Smith-Magenis syndrome. Hum Genet 109:535-41

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