Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS) is a heterogeneous developmental disorder characterized by facial dysmorphia, upper limb defects, hirsutism, and gastrointestinal abnormalities. About 65% of patients harbor mutations in genes that encode subunits or regulators of the cohesin complex, including NIPBL, SMC1A, SMC3, RAD21, and HDAC8.

Congenital malformation

NIPBL [HSA:25836] [KO:K06672]
SMC1A [HSA:8243] [KO:K06636]
SMC3 [HSA:9126] [KO:K06669]
RAD21 [HSA:5885] [KO:K06670]
HDAC8 [HSA:55869] [KO:K11405]

PMID:19793304 (gene, desription)

Liu J, Krantz ID

Cornelia de Lange syndrome, cohesin, and beyond.

Clin Genet 76:303-14 (2009)
DOI:10.1111/j.1399-0004.2009.01271.x

PMID:19842212

Mannini L, Liu J, Krantz ID, Musio A

Spectrum and consequences of SMC1A mutations: the unexpected involvement of a core component of cohesin in human disease.

Hum Mutat 31:5-10 (2010)
DOI:10.1002/humu.21129

PMID:18996922

Revenkova E, Focarelli ML, Susani L, Paulis M, Bassi MT, Mannini L, Frattini A, Delia D, Krantz I, Vezzoni P, Jessberger R, Musio A

Cornelia de Lange syndrome mutations in SMC1A or SMC3 affect binding to DNA.

Hum Mol Genet 18:418-27 (2009)
DOI:10.1093/hmg/ddn369

PMID:20727427

Ratajska M, Wierzba J, Pehlivan D, Xia Z, Brundage EK, Cheung SW, Stankiewicz P, Lupski JR, Limon J

Cornelia de Lange syndrome case due to genomic rearrangements including NIPBL.

Eur J Med Genet 53:378-82 (2010)
DOI:10.1016/j.ejmg.2010.08.002

PMID:22633399

Deardorff MA, Wilde JJ, Albrecht M, Dickinson E, Tennstedt S, Braunholz D, Monnich M, Yan Y, Xu W, Gil-Rodriguez MC, Clark D, Hakonarson H, Halbach S, Michelis LD, Rampuria A, Rossier E, Spranger S, Van Maldergem L, Lynch SA, Gillessen-Kaesbach G, Ludecke HJ, Ramsay RG, McKay MJ, Krantz ID, Xu H, Horsfield JA, Kaiser FJ

RAD21 mutations cause a human cohesinopathy.

Am J Hum Genet 90:1014-27 (2012)
DOI:10.1016/j.ajhg.2012.04.019

PMID:22885700

Deardorff MA, Bando M, Nakato R, Watrin E, Itoh T, Minamino M, Saitoh K, Komata M, Katou Y, Clark D, Cole KE, De Baere E, Decroos C, Di Donato N, Ernst S, Francey LJ, Gyftodimou Y, Hirashima K, Hullings M, Ishikawa Y, Jaulin C, Kaur M, Kiyono T, Lombardi PM, Magnaghi-Jaulin L, Mortier GR, Nozaki N, Petersen MB, Seimiya H, Siu VM, Suzuki Y, Takagaki K, Wilde JJ, Willems PJ, Prigent C, Gillessen-Kaesbach G, Christianson DW, Kaiser FJ, Jackson LG, Hirota T, Krantz ID, Shirahige K

HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.

Nature 489:313-7 (2012)
DOI:10.1038/nature11316

PMID:25574841

Yuan B, Pehlivan D, Karaca E, Patel N, Charng WL, Gambin T, Gonzaga-Jauregui C, Sutton VR, Yesil G, Bozdogan ST, Tos T, Koparir A, Koparir E, Beck CR, Gu S, Aslan H, Yuregir OO, Al Rubeaan K, Alnaqeb D, Alshammari MJ, Bayram Y, Atik MM, Aydin H, Geckinli BB, Seven M, Ulucan H, Fenercioglu E, Ozen M, Jhangiani S, Muzny DM, Boerwinkle E, Tuysuz B, Alkuraya FS, Gibbs RA, Lupski JR

Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.

J Clin Invest 125:636-51 (2015)
DOI:10.1172/JCI77435