Cornelia de Lange Syndrome Publications

The following articles show CHOP’s significant contributions to the field over recent years.

Mutation spectrum and genotype-phenotype correlation in Cornelia de Lange Syndrome. Mannini L, Cucco F, Quarantotti V, Krantz ID, Musio A. Hum Mutat. 2013;34(12):1589-1596.

Immunologic features of Cornelia de Lange syndrome. Jyonouchi S, Orange J, Sullivan KE, Krantz I, Deardorff M. Pediatrics. 2013;132(2):e484-489.

HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. 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. Nature. 2012;489(7415):313-317.

Congenital heart disease in Cornelia de Lange syndrome: phenotype and genotype analysis. Chatfield KC, Schrier SA, Li J, Clark D, Kaur M, Kline AD, Deardorff MA, Jackson LS, Goldmuntz E, Krantz ID. Am J Med Genet. 2012;158A(10):2499-2505.

Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization. Descipio C, Conlin L, Rosenfeld J, Tepperberg J, Pasion R, Patel A, McDonald MT, Aradhya S, Ho D, Goldstein J, McGuire M, Mulchandani S, Medne L, Rupps R, Serrano AH, Thorland EC, Tsai AC, Hilhorst-Hofstee Y, Ruivenkamp CA, Van Esch H, Addor MC, Martinet D, Mason TB, Clark D, Spinner NB, Krantz ID. Am J Med Genet. 2012;158A(9):2152-2161.

Identification of a profile of Cornelia de Lange syndrome (CdLS): a review of 53 CdLS pregnancies. Clark DM, Sherer I, Deardorff MA, Byrne JL, Loomes KM, Nowaczyk MJ, Jackson LG, Krantz ID. Am J Med Genet.2012;158A(8):1848-56.

Investigation of autistic features among individuals with mild to moderate Cornelia de Lange syndrome. Nakanishi M, Deardorff MA, Clark D, Levy SE, Krantz I, Pipan M. Am J Med Genet. 2012;158A(8):1841-1847.

RAD21 mutations cause a human cohesinopathy. Deardorff MA, Wilde JJ, Albrecht M, Dickinson E, Tennstedt S, Braunholz D, Mönnich M, Yan Y, Xu W, Gil-Rodríguez MC, Clark D, Hakonarson H, Halbach S, Michelis LD, Rampuria A, Rossier E, Spranger S, Van Maldergem L, Lynch SA, Gillessen-Kaesbach G, Lüdecke HJ, Ramsay RG, McKay MJ, Krantz ID, Xu H, Horsfield JA, Kaiser FJ. Am J Med Genet. 2012;90(6):1014-1027.

Germline mosaicism in Cornelia de Lange syndrome. Slavin TP, Lazebnik N, Clark DM, Vengoechea J, Cohen L, Kaur M, Konczal L, Crowe CA, Corteville JE, Nowaczyk MJ, Byrne JL, Jackson LG, Krantz ID. Am J Med Genet. 2012;158A(6):1481-1485.

Occurrence and clinical features of epileptic and non-epileptic paroxysmal events in five children with Pallister-Killian syndrome. Filloux FM, Carey JC, Krantz ID, Ekstrand JJ, Candee MS. Eur J Med Genet. 2012;55(5):367-373.

NIPBL rearrangements in Cornelia de Lange syndrome: evidence for replicative mechanism and genotype-phenotype correlation. Pehlivan D, Hullings M, Carvalho CM, Gonzaga-Jauregui CG, Loy E, Jackson LG, Krantz ID, Deardorff MA, Lupski JR. Genet Med. 2012;14(3):313-322.

Proteomic Profile Identifies Dysregulated Pathways in Cornelia de Lange Syndrome Cells with Distinct Mutations in SMC1A and SMC3 Genes. Gimigliano A, Mannini L, Bianchi L, Puglia M, Deardorff MA, Menga S, Krantz ID, Musio A, Bini L. J Proteome Res. Published online: November 5, 2012.

This study enabled further discovery of specific biochemical pathways related to SMC1A and SMC3 gene mutations that supports the clinical features seen in individuals with CdLS.

HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. 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. Nature. 2012;489(7415):313-317.

Mutations in the X-linked gene, HDAC8, have been identified in six individuals with CdLS who presented with facial features as well as growth and cognitive delay consistent with those caused by mutations in NIPBL or “classical” CdLS.

Congenital heart disease in Cornelia de Lange syndrome: phenotype and genotype analysis. Chatfield KC, Schrier SA, Li J, Clark D, Kaur M, Kline AD, Deardorff MA, Jackson LS, Goldmuntz E, Krantz ID. Am J Med Genet. 2012;158A(10):2499-3505.

Congenital heart disease (CHD) is present in 14 to 70 percent of individuals with CdLS. This study evaluated the trends of CHD seen in the CdLS population and found that structural CHDs were more likely to be present in individuals with a moderate and severe CdLS presentation.

Identification of a prenatal profile of Cornelia de Lange syndrome (CdLS): a review of 53 CdLS pregnancies. Clark DM, Sherer I, Deardorff MA, Byrne JL, Loomes KM, Nowaczyk MJ, Jackson LG, Krantz ID. Am J Med Genet. 2012;158A(8): 1848-1856.

Currently, there are no definitive prenatal screening measures available for a prenatal diagnosis of CdLS. This study analyzed 53 cases of prenatal CdLS findings to reveal a pattern of sonographic features and maternal serum markers which may allow for the diagnosis of CdLS prenatally.

Investigation of autistic features among individuals with mild to moderate Cornelia de Lange syndrome. Nakanishi M, Deardorff MA, Clark D, Levy SE, Krantz I, Pipan M. Am J Med Genet. 2012;158A(8):1841-1847.

Autism has been frequently reported in CdLS, and this study investigates autistic features in individuals with a mild to moderate presentation of CdLS. Autistic features were found to occur in 43 percent of individuals in the studied cohort.

RAD21 mutations cause a human cohesinopathy. Deardorff MA, Wilde JJ, Albrecht M, Dickinson E, Tennstedt S, Braunholz D, Mönnich M, Yan Y, Xu W, Gil-Rodríguez MC, Clark D, Hakonarson H, Halbach S, Michelis LD, Rampuria A, Rossier E, Spranger S, Van Maldergem L, Lynch SA, Gillessen-Kaesbach G, Lüdecke HJ, Ramsay RG, McKay MJ, Krantz ID, Xu H, Horsfield JA, Kaiser FJ. Am J Med Genet. 2012;90(6):1014-1027.

Individuals with mutations in RAD21 were found to have clinical features which overlap with CdLS, including short stature and facial features. These individuals were also noted to have a milder cognitive impairment compared to individuals with classical CdLS.

Germline mosaicism in Cornelia de Lange syndrome. Slavin TP, Lazebnik N, Clark DM, Vengoechea J, Cohen L, Kaur M, Konczal L, Crowe CA, Corteville JE, Nowaczyk MJ, Byrne JL, Jackson LG, Krantz ID. Am J Med Genet. 12012;58A(6):1481-1485.

Germline mosaicism is a described mechanism for CdLS occurrence when there are several affected offspring of unaffected parents. Risk of recurrence of CdLS occurring in a future pregnancy to clinically unaffected parents has been previously estimated to be as high as 1.5 percent. This number may be an underrepresentation as germline mosaicism cases ranged from 3.4 percent to 5.4 percent of the total studied cohort.

NIPBL rearrangements in Cornelia de Lange syndrome: evidence for replicative mechanism and genotype-phenotype correlation. Pehlivan D, Hullings M, Carvalho CM, Gonzaga-Jauregui CG, Loy E, Jackson LG, Krantz ID, Deardorff MA, Lupski JR. Genet Med. 2012;14(3):313-322.

Of 162 patients with CdLS who had negative testing for NIPBL by sequencing, seven individuals had deletions of NIPBL exons. This study shows there is clinical utility in testing for copy number variations when NIPBL studies by DNA-sequencing are mutation negative.

Causes of death and autopsy findings in a large study cohort of individuals with Cornelia de Lange syndrome and review of the literature. Schrier SA, Sherer I, Deardorff MA, Clark D, Audette L, Gillis L, Kline AD, Ernst L, Loomes K, Krantz ID, Jackson LG. Am J Med Genet. 2011;155A(12):3007-3024.

This comprehensive review has identified important etiologies contributing to our understanding of clinical complications, management, and avoidance of morbidity and mortality in this population.

Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization. Descipio C, Conlin L, Rosenfeld J, Tepperberg J, Pasion R, Patel A, McDonald MT, Aradhya S, Ho D, Goldstein J, McGuire M, Mulchandani S, Medne L, Rupps R, Serrano AH, Thorland EC, Tsai AC, Hilhorst-Hofstee Y, Ruivenkamp CA, Van Esch H, Addor MC, Martinet D, Mason TB, Clark D, Spinner NB, Krantz ID. Am J Med Genet. 2012;158A(9):2152-2161.

This study evaluates the clinical history and molecular cytogenetic findings of individuals with deletions involving the short arm of chromosome 10 (region 10p15.3). Molecular characterization of these individuals suggests that two genes, ZMYND11 and DIP2C, contribute to the clinical features including cognitive differences, craniofacial characteristics and low muscle tone, as well as speech and motor delay.

Isolated NIPBL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction. Braunholz D, Hullings M, Gil-Rodríguez MC, Fincher CT, Mallozzi MB, Loy E, Albrecht M, Kaur M, Limon J, Rampuria A, Clark D, Kline A, Dalski A, Eckhold J, Tzschach A, Hennekam R, Gillessen-Kaesbach G, Wierzba J, Krantz ID, Deardorff MA, Kaiser FJ. Eur J Hum Genet. 2011;20(3):271-6.

Certain mutations in NIPBL affect the function of the protein, MAU2, which is important in cohesin function. This data suggests that MAU2, as well as additional factors, are essential in determining clinical features and severity of CdLS.

Genome-wide DNA methylation analysis in cohesin mutant human cell lines. Liu J, Zhang Z, Bando M, Itoh T, Deardorff MA, Li JR, Clark D, Kaur M, Tatsuro K, Kline AD, Chang C, Vega H, Jackson LG, Spinner NB, Shirahige K, Krantz ID. Nucleic Acids Res. 2010;38(17):5657-5671.

Analysis suggests that DNA methylation as well as other mechanisms are involved in the regulation of gene transcription and subsequent misregulation responsible for causing CdLS.