Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome.
Cornelia de Lange syndrome (CdLS) manifests facial dysmorphic features, growth and cognitive impairment, and limb malformations. Mutations in three genes (NIPBL, SMC1A, and SMC3) of the cohesin complex and its regulators have been found in affected patients. Here, we present clinical and molecular characterization of 30 unrelated patients with CdLS. Eleven patients had mutations in NIPBL (37%) and three patients had mutations in SMC1A (10%), giving an overall rate of mutations of 47%. Several patients shared the same mutation in NIPBL (p.R827GfsX2) but had variable phenotypes, indicating the influence of modifiers in CdLS. Patients with NIPBL mutations had a more severe phenotype than those with mutations in SMC1A or those without identified mutations. However, a high incidence of palate defects was noted in patients with SMC1A mutations. In addition, we observed a similar phenotype in both male and female patients with SMC1A mutations. Finally, we report the first patient with an SMC1A mutation and the Sandifer complex.
Pié
Juan
J
Laboratory of Clinical Genetics and Functional Genomics, Department of Pharmacology, Medical School, University of Zaragoza, Zaragoza, Spain. juanpie@unizar.es
Gil-Rodríguez
María Concepción
MC
Ciero
Milagros
M
López-Viñas
Eduardo
E
Ribate
María Pilar
MP
Arnedo
María
M
Deardorff
Matthew A
MA
Puisac
Beatriz
B
Legarreta
Jesús
J
de Karam
Juan Carlos
JC
Rubio
Encarnación
E
Bueno
Inés
I
Baldellou
Antonio
A
Calvo
M Teresa
MT
Casals
Nuria
N
Olivares
José Luis
JL
Losada
Ana
A
Hegardt
Fausto G
FG
Krantz
Ian D
ID
Gómez-Puertas
Paulino
P
Ramos
Feliciano J
FJ
D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D015331:Cohort Studies; D003635:De Lange Syndrome / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D000098550:Structural Maintenance of Chromosome Protein 1
D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; C487465:NIPBL protein, human; D011506:Proteins; C492318:SMC3 protein, human; D000098550:Structural Maintenance of Chromosome Protein 1