| NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes. | |
MedLine Citation:
|
PMID: 12464997 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Sotos syndrome is a childhood overgrowth syndrome characterized by a distinctive facial appearance, height and head circumference >97th percentile, advanced bone age, and developmental delay. Weaver syndrome is characterized by the same criteria but has its own distinctive facial gestalt. Recently, a 2.2-Mb chromosome 5q35 microdeletion, encompassing NSD1, was reported as the major cause of Sotos syndrome, with intragenic NSD1 mutations identified in a minority of cases. We evaluated 75 patients with childhood overgrowth, for intragenic mutations and large deletions of NSD1. The series was phenotypically scored into four groups, prior to the molecular analyses: the phenotype in group 1 (n=37) was typical of Sotos syndrome; the phenotype in group 2 (n=13) was Sotos-like but with some atypical features; patients in group 3 (n=7) had Weaver syndrome, and patients in group 4 (n=18) had an overgrowth condition that was neither Sotos nor Weaver syndrome. We detected three deletions and 32 mutations (13 frameshift, 8 nonsense, 2 splice-site, and 9 missense) that are likely to impair NSD1 functions. The truncating mutations were spread throughout NSD1, but there was evidence of clustering of missense mutations in highly conserved functional domains between exons 13 and 23. There was a strong correlation between presence of an NSD1 alteration and clinical phenotype, in that 28 of 37 (76%) patients in group 1 had NSD1 mutations or deletions, whereas none of the patients in group 4 had abnormalities of NSD1. Three patients with Weaver syndrome had NSD1 mutations, all between amino acids 2142 and 2184. We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes. |
Authors:
|
Jenny Douglas; Sandra Hanks; I Karen Temple; Sally Davies; Alexandra Murray; Meena Upadhyaya; Susan Tomkins; Helen E Hughes; Trevor R P Cole; Nazneen Rahman |
Related Documents
:
|
16970037 - Heterogeneity of the triple a syndrome and assessment of a case. 12719077 - Spondylo-ocular syndrome: a new entity with crystalline lens malformation, cataract, re... 20550487 - Amyotrophic lateral sclerosis in a patient with kartagener syndrome. 12408187 - A secondary respiratory chain defect in a patient with fanconi-bickel syndrome. 12064787 - Articulation in prader-willi syndrome. 20952877 - Bilateral pigmented hairy epidermal naevus. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2002-12-02 |
Journal Detail:
|
Title: American journal of human genetics Volume: 72 ISSN: 0002-9297 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 2003 Jan |
Date Detail:
|
Created Date: 2002-12-18 Completed Date: 2003-02-21 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: United States |
Other Details:
|
Languages: eng Pagination: 132-43 Citation Subset: IM |
Affiliation:
|
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom. |
| Data Bank Information | |
Bank Name/Acc. No.:
|
GENBANK/AF083389; AF332469; AF395588; AF419220; OMIM/117550; 130650; 153470; 162200; 182290; 194050; 277590; 312870; 602535; 605309 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Abnormalities, Multiple
/
genetics* Amino Acid Sequence Carrier Proteins / chemistry, genetics* Child Chromosome Deletion Chromosomes, Human, Pair 5 / genetics Craniofacial Abnormalities / genetics* DNA Mutational Analysis Developmental Disabilities / genetics Exons / genetics Female Growth Disorders / genetics* Humans Intracellular Signaling Peptides and Proteins* Introns / genetics Male Molecular Sequence Data Mutation / genetics* Nuclear Proteins / chemistry, genetics* Pedigree Phenotype Polymorphism, Genetic / genetics Protein Structure, Tertiary Sequence Deletion / genetics Syndrome |
| Chemical | |
Reg. No./Substance:
|
0/Carrier Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/NSD1 protein, human; 0/Nuclear Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Ovarian thecoma associated with a large quantity of ascites and elevated serum CA 125 and CA 15-3.
Next Document: Clinical evaluation of patients with temporomandibular joint implants.