Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype.

Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Research Abstract Details 

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Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Abstract Text:

Lorraine Potocki,Weimin Bi,Diane Treadwell-Deering,Claudia M B Carvalho,Anna Eifert,Ellen M Friedman,Daniel Glaze,Kevin Krull,Jennifer A Lee,Richard Alan Lewis,Roberto Mendoza-Londono,Patricia Robbins-Furman,Chad Shaw,Xin Shi,George Weissenberger,Marjorie Withers,Svetlana A Yatsenko,Elaine H Zackai,Pawel Stankiewicz,James R Lupski,

The duplication 17p11.2 syndrome, associated with dup(17)(p11.2p11.2), is a recently recognized syndrome of multiple congenital anomalies and mental retardation and is the first predicted reciprocal microduplication syndrome described--the homologous recombination reciprocal of the Smith-Magenis syndrome (SMS) microdeletion (del(17)(p11.2p11.2)). We previously described seven subjects with dup(17)(p11.2p11.2) and noted their relatively mild phenotype compared with that of individuals with SMS. Here, we molecularly analyzed 28 additional patients, using multiple independent assays, and also report the phenotypic characteristics obtained from extensive multidisciplinary clinical study of a subset of these patients. Whereas the majority of subjects (22 of 35) harbor the homologous recombination reciprocal product of the common SMS microdeletion (~3.7 Mb), 13 subjects (~37%) have nonrecurrent duplications ranging in size from 1.3 to 15.2 Mb. Molecular studies suggest potential mechanistic differences between nonrecurrent duplications and nonrecurrent genomic deletions. Clinical features observed in patients with the common dup(17)(p11.2p11.2) are distinct from those seen with SMS and include infantile hypotonia, failure to thrive, mental retardation, autistic features, sleep apnea, and structural cardiovascular anomalies. We narrow the critical region to a 1.3-Mb genomic interval that contains the dosage-sensitive RAI1 gene. Our results refine the critical region for Potocki-Lupski syndrome, provide information to assist in clinical diagnosis and management, and lend further support for the concept that genomic architecture incites genomic instability.

Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Publishing Authors By Initials

L Potocki,W Bi,D Treadwell-Deering,CM Carvalho,A Eifert,EM Friedman,D Glaze,K Krull,JA Lee,RA Lewis,R Mendoza-Londono,P Robbins-Furman,C Shaw,X Shi,G Weissenberger,M Withers,SA Yatsenko,EH Zackai,P Stankiewicz,JR Lupski,

For similar pathological conditions, signs and symptoms: pathologic processes: disease: syndrome research abstracts see: pathological conditions, signs and symptoms: pathologic processes: disease: syndrome research

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Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of human genetics

VOLUME: 80

Page Numbers: 633-49

Journal Abbreviation: Am. J. Hum. Genet.

ISSN: 0002-9297

DAY: 26

MONTH: 02

YEAR: 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. Information

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LANGUAGE: eng

NlmUniqueID: 370475

Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Keywords Mesh Terms:

KEYWORDS: Syndrome

MESH TERMS: genetics

Chemical & Substance for Abstract: Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Information

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Grant and Affiliation Information for Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype.

AFFILIATION: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Country: United States

AGENCY: United States NICHD

GRANT: P01 HD39420

ACRONYM: HD

MEDLINETA: Am J Hum Genet

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