Cornelia de Lange syndrome case due to genomic rearrangements including NIPBL.
Cornelia de Lange syndrome (CdLS) is a rare multisystem congenital anomaly disorder characterized by growth and developmental delay, distinctive facial dysmorphism, limb malformations and multiple organ defects. Approximately 60-65% of the CdLS subjects have mutation in one of three cohesin proteins, a main regulator of cohesin-associated protein, NIPBL, and two components of the cohesin ring structure SMC1A and SMC3. A prominent role for cohesin is to control chromosome segregation during cell divisions. We have performed MLPA analysis in a group of 11 children with the CdLS but without identifiable point mutations in the NIPBL and SMC1A genes. In a single patient, we identified a large deletion encompassing exons 35 to 47 of the NIPBL gene. Our finding was validated by aCGH and further characterized by long-range PCR and DNA sequencing of the breakpoint junction.
Ratajska
Magdalena
M
Department of Biology and Genetics, Medical University of Gdansk, Poland.
Wierzba
Jolanta
J
Pehlivan
Davut
D
Xia
Zhilian
Z
Brundage
Ellen K
EK
Cheung
Sau Wai
SW
Stankiewicz
Pawel
P
Lupski
James R
JR
Limon
Janusz
J
D000293:Adolescent; D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004252:DNA Mutational Analysis; D003635:De Lange Syndrome / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D021141:Nucleic Acid Amplification Techniques; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D055815:Young Adult; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D011506:Proteins; D000097722:Cohesins; C487465:NIPBL protein, human