Document Detail

Heterogeneity of NSD1 alterations in 116 patients with Sotos syndrome.
MedLine Citation:
PMID:  17565729     Owner:  NLM     Status:  MEDLINE    
Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features, learning difficulties, and macrocephaly with frequent pre- and postnatal overgrowth with advanced bone age. Here, we report on our experience in the molecular diagnostic of Sotos syndrome on 116 patients. Using direct sequencing and a quantitative multiplex PCR of short fluorescent fragments (QMPSF)-based assay allowing accurate detection of both total and partial NSD1 deletions, we identified NSD1 abnormalities in 104 patients corresponding to 102 Sotos families (90%). NSD1 point mutations were detected in 80% of the index cases, large deletions removing the NSD1 gene entirely in 14%, and intragenic NSD1 rearrangements in 6%. Among the 69 detected distinct point mutations, 48 were novel. The QMPSF assay detected an exonic duplication and a mosaic partial deletion. QMPSF mapping of the 15 large deletions revealed the heterogeneity of the deletions, which vary in size from 1 to 4.5 Mb. Clinical features of NSD1-positive Sotos patients revealed that the phenotype in patients with nontruncating mutations was less severe that in patients with truncating mutations. This study confirms the heterogeneity of NSD1 alterations in Sotos syndrome and therefore the need to complete sequencing analysis by screening for partial deletions and duplications to ensure an accurate molecular diagnosis of this syndrome.
Pascale Saugier-Veber; Céline Bonnet; Alexandra Afenjar; Valérie Drouin-Garraud; Christine Coubes; Séverine Fehrenbach; Muriel Holder-Espinasse; Joëlle Roume; Valérie Malan; Marie-France Portnoi; Nicolas Jeanne; Clarisse Baumann; Delphine Héron; Albert David; Marion Gérard; Dominique Bonneau; Didier Lacombe; Valérie Cormier-Daire; Thierry Billette de Villemeur; Thierry Frébourg; Lydie Bürglen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Human mutation     Volume:  28     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-22     Completed Date:  2007-11-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1098-107     Citation Subset:  IM    
Copyright Information:
2007 Wiley-Liss, Inc.
Department of Genetics, Rouen University Hospital, University of Rouen, Rouen, France.
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MeSH Terms
Abnormalities, Multiple / genetics*
Child, Preschool
Genetic Heterogeneity*
Infant, Newborn
Intracellular Signaling Peptides and Proteins / genetics*
Nuclear Proteins / genetics*
Polymerase Chain Reaction
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/NSD1 protein, human; 0/Nuclear Proteins

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