A syndrome of short stature, microcephaly and speech delay is associated with duplications reciprocal to the common Sotos syndrome deletion.
Genomic rearrangements are an increasingly recognized mechanism of human phenotypic variation and susceptibility to disease. Sotos syndrome is characterized by overgrowth, macrocephaly, developmental delay and advanced osseous maturation. Haploinsufficiency of NSD1, caused by inactivating point mutations or deletion copy number variants, is the only known cause of Sotos syndrome. A recurrent 2 Mb deletion has been described with variable frequency in different populations. In this study, we report two individuals of different ethnic and geographical backgrounds, with duplications reciprocal to the common Sotos syndrome deletion. Our findings provide evidence for the existence of a novel syndrome of short stature, microcephaly, delayed bone development, speech delay and mild or absent facial dysmorphism. The phenotype is remarkably opposite to that of Sotos syndrome, suggesting a role for NSD1 in the regulation of somatic growth in humans.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Luis M
LM
Franco
Thomy
T
de Ravel
Brett H
BH
Graham
Stephanie M
SM
Frenkel
Jozef
J
Van Driessche
Pawel
P
Stankiewicz
James R
JR
Lupski
Joris R
JR
Vermeesch
Sau Wai
SW
Cheung
D000328:Adult; D001827:Body Height / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D002658:Developmental Disabilities / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D015321:Gene Rearrangement; D014644:Genetic Variation; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007805:Language Development Disorders / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D056916:Segmental Duplications, Genomic; D017384:Sequence Deletion; D013577:Syndrome
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human