Mutational and genotype-phenotype correlation analyses in 28 Polish patients with Cornelia de Lange syndrome.
Cornelia de Lange syndrome (CdLS) is a multisystem congenital anomaly disorder characterized by prenatal and postnatal growth retardation, developmental delay, distinctive facial dysmorphism, limb malformations, and multiple organ defects. Mutations in the NIPBL gene have been discovered recently as a major etiology for this syndrome, and were detected in 27-56% of patients. Two groups have found significant differences in the severity or penetrance of some phenotypes between mutation positive and mutation negative patients. Different clinical features have also been described among patients with missense versus truncating mutations. In this study, we identified 13 NIPBL mutations in 28 unrelated Polish CdLS patients (46.4%), 11 were novel. Mutation positive patients were more severely affected in comparison to mutation negative individuals with respect to weight, height, and mean head circumference at birth, facial dysmorphism and speech impairment. Analyses of combined data from this and the two previous studies revealed that the degree of growth, developmental delay and limb defects showed significant differences between patients with and without mutations and between patients with missense and truncating mutations, whereas only a portion of these features differed significantly in any individual study. Furthermore, bioinformatic analyses of the NIPBL protein revealed several novel domains, which may give further clues about potential functions of this protein.
Yan
Jiong
J
Department of Molecular and Human Genetics, Houston, Texas, USA.
Saifi
Gulam Mustafa
GM
Wierzba
Tomasz H
TH
Withers
Marjorie
M
Bien-Willner
Gabriel A
GA
Limon
Janusz
J
Stankiewicz
Paweł
P
Lupski
James R
JR
Wierzba
Jolanta
J
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D003635:De Lange Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011044:Poland; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D017384:Sequence Deletion
D018797:Cell Cycle Proteins; C487465:NIPBL protein, human; D011506:Proteins; D004247:DNA