| Duplication of chromosome band 12q24.11q24.23 results in apparent Noonan syndrome. | |
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MedLine Citation:
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PMID: 18348260 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Noonan syndrome is an autosomal dominant disorder with an estimated incidence of 1 in 1,000 to 1 in 2,500 live births. It is characterized by postnatal-onset short stature, characteristic facial changes, webbed neck, pectus carinatum, or excavatum, congenital heart defects, and bleeding abnormalities. Gain-of-function mutations in the PTPN11, KRAS, SOS1, and RAF1 genes that are components of the RAS/MEPK signaling pathway are identified in about 70-85% of individuals with Noonan syndrome. We report here a case of duplication of chromosome region 12q24.11q24.23 identified by array comparative genomic hybridization (aCGH) that includes the PTPN11 gene in a 3-year-old girl with apparent Noonan syndrome. The patient presented with postnatal-onset failure-to-thrive, developmental delay, microcephaly, velopalatal incompetence, pectus excavatum, coarctation of aorta, atrial and ventricular septal defects, decreased muscle tone, and minor facial anomalies consistent with Noonan syndrome. At 3 years of age her speech, gross and fine motor development were at the level of a 12-18 month old child. This degree of developmental delay was atypical for an individual with Noonan syndrome, raising concerns for a chromosomal abnormality. Array-CGH showed an interstitial duplication of 10 Mb including the PTPN11 gene. Sequencing of PTPN11, KRAS, SOS1 and the coding region of RAF1 did not identify mutations. The increased gene dosage of the PTPN11 gene in the form of duplication is expected to have the same consequence as gain-of-function mutations seen in Noonan syndrome. We propose that at least some of the 15-30% of individuals with Noonan syndrome who do not have a mutation by sequencing may have a gain in copy number of PTPN11 and recommend that comprehensive testing for Noonan syndrome should include analysis for copy number changes of PTPN11. |
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Authors:
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Oleg A Shchelochkov; Ankita Patel; George M Weissenberger; A Craig Chinault; Joanna Wiszniewska; Priscilla H Fernandes; Christine Eng; Mary K Kukolich; V Reid Sutton |
Publication Detail:
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Type: Case Reports; Journal Article |
Journal Detail:
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Title: American journal of medical genetics. Part A Volume: 146A ISSN: 1552-4833 ISO Abbreviation: Am. J. Med. Genet. A Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-04-02 Completed Date: 2008-04-29 Revised Date: 2008-05-21 |
Medline Journal Info:
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Nlm Unique ID: 101235741 Medline TA: Am J Med Genet A Country: United States |
Other Details:
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Languages: eng Pagination: 1042-8 Citation Subset: IM |
Copyright Information:
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Copyright 2008 Wiley-Liss, Inc. |
Affiliation:
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Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Child, Preschool Chromosome Banding* Chromosomes, Human, Pair 12 / genetics* Female Gene Dosage Gene Duplication* Humans Noonan Syndrome / genetics*, physiopathology Nucleic Acid Hybridization / methods Oligonucleotide Array Sequence Analysis / methods Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics |
| Chemical | |
Reg. No./Substance:
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EC 3.1.3.48/PTPN11 protein, human; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 11 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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