Genome-wide SNP array analysis in patients with features of sotos syndrome.
BACKGROUND
Sotos syndrome is characterized by overgrowth, facial dysmorphism and learning impairment. Haploinsufficiency of NSD1 accounts for approximately 60-90% of the patients. Consequently, a considerable number of patients with features of Sotos syndrome remain without a molecular diagnosis. To date, target-gene approaches in these patients have not been successful.


METHODS
Twenty-six Sotos syndrome-like patients were analyzed with a high-resolution whole-genome SNP array, and segregation was studied in the parents.


RESULTS
Four possible pathogenic copy-number variants including deletions of 10p12.32-p12.31, 14q13.1, Xq21.1-q21.31 and a duplication of 15q11.2-q13.1 were detected. They varied in size from 155 kb to 13.36 Mb. The 10p12.32-p12.31 deletion revealed a candidate gene (PLXDC2) for overgrowth. The 14q13.1 deletion affected only the NPAS3 gene and the patient carrying this deletion displayed mental retardation as the main feature. The Xq21.1-q21.31 deletion and the 15q11.2-q13.1 duplication encompassed multiple genes of which several could be associated with phenotypic expression.


CONCLUSIONS
The high-resolution genome-wide SNP array approach resulted in a detection rate of 15% of novel abnormalities and is therefore a powerful method to attain a molecular diagnosis in Sotos syndrome-like patients. Identified candidate genes provide directions for future screening of larger patient cohorts.
Visser
Remco
R
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. r.visser @ lumc.nl
Gijsbers
Antoinet
A
Ruivenkamp
Claudia
C
Karperien
Marcel
M
Reeser
H Maarten
HM
Breuning
Martijn H
MH
Kant
Sarina G
SG
Wit
Jan M
JM
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019066:Facies; D005260:Female; D055106:Genome-Wide Association Study; D005877:Gigantism / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome; D049951:X Chromosome Inactivation; D055815:Young Adult
D004247:DNA