J Pediatr Genet 2022; 11(03): 245-252
DOI: 10.1055/s-0040-1718534
Case Report

A Novel Mutation in NIPBL Gene with the Cornelia de Lange Syndrome and a 10q11.22-q11.23 Microdeletion in the Same Individual

1   Department of Medical Genetics, Medical School of Adiyaman University, Adiyaman, Turkey
,
Özden Öztürk
1   Department of Medical Genetics, Medical School of Adiyaman University, Adiyaman, Turkey
,
Semih Bolu
2   Division of Pediatric Endocrinology, Department of Pediatrics, Medical School of Adiyaman University, Adiyaman, Turkey
,
Bayram Taşkın
3   Department of Medical Genetics, Haseki Education and Research Hospital, İstanbul, Turkey
› Author Affiliations
Funding None.

Abstract

The Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. CdLS is due to mutations in one of the following genes: NIPBL, SMC1A, SMC3, RAD21, and HDAC8. On the other hand, 10q11.2 deletions cause a wide range of presentations in patients. Approximately 40 cases with variable deletions of 10q11.2 have been reported in literature. Some of the reported cases involve the coexistence of duplication or deletion affecting one copy of the chromosome. However, deletion of chromosome 10q11.22-q11.23 and CdLS syndrome caused by NIPBL gene mutations have not been reported previously. This report, therefore, is the first to report their coexistence together.

Availability of Data and Materials

All data used in this study are available from the corresponding author on reasonable request.


Authors' Contributions

H.B. and Ö.Ö. designed the study; S.B. and Ö.Ö. made the examination of the patient and family; H.B. and Ö.Ö. wrote manuscript. B.T. performed the genetic studies. All authors read and approved the final manuscript.




Publication History

Received: 19 June 2020

Accepted: 01 September 2020

Article published online:
15 October 2020

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  • References

  • 1 Liu J, Baynam G. Cornelia de Lange syndrome. Adv Exp Med Biol 2010; 685: 111-123
  • 2 Ireland M, Donnai D, Burn J. Brachmann-de Lange syndrome. Delineation of the clinical phenotype. Am J Med Genet 1993; 47 (07) 959-964
  • 3 Kline AD, Barr M, Jackson LG. Growth manifestations in the Brachmann-de Lange syndrome. Am J Med Genet 1993; 47 (07) 1042-1049
  • 4 Kline AD, Krantz ID, Deardorff MA. et al. Cornelia de Lange syndrome and molecular implications of the cohesin complex: abstracts from the 7th biennial scientific and educational symposium 2016. Am J Med Genet A 2017; 173 (05) 1172-1185
  • 5 Ayerza Casas A, Puisac Uriol B, Teresa Rodrigo ME, Hernández Marcos M, Ramos Fuentes FJ, Pie Juste J. [ Cornelia de Lange syndrome: congenital heart disease in 149 patients] (in Spanish). Med Clin (Barc) 2017; 149 (07) 300-302
  • 6 Avagliano L, Grazioli P, Mariani M, Bulfamante GP, Selicorni A, Massa V. Integrating molecular and structural findings: Wnt as a possible actor in shaping cognitive impairment in Cornelia de Lange syndrome. Orphanet J Rare Dis 2017; 12 (01) 174
  • 7 Cao R, Pu T, Fang S. et al. Patients carrying 9q31.1-q32 deletion share common features with Cornelia de Lange Syndrome. Cell Physiol Biochem 2015; 35 (01) 270-280
  • 8 Stankiewicz P, Kulkarni S, Dharmadhikari AV. et al. Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats. Hum Mutat 2012; 33 (01) 165-179
  • 9 Schwartz M, Sternberg D, Whalen S. et al. How chromosomal deletions can unmask recessive mutations? Deletions in 10q11.2 associated with CHAT or SLC18A3 mutations lead to congenital myasthenic syndrome. Am J Med Genet A 2018; 176 (01) 151-155
  • 10 Sue Richards, Nazneen Aziz, Sherri Bale, David Bick, Soma Das, Julie Gastier-Foster Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (05) 405-424 DOI: 10.1038/gim.2015.30.
  • 11 Tonkin ET, Wang TJ, Lisgo S, Bamshad MJ, Strachan T. NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome. Nat Genet 2004; 36 (06) 636-641
  • 12 Dorsett D. The Drosophila melanogaster model for Cornelia de Lange syndrome: Implications for etiology and therapeutics. Am J Med Genet C Semin Med Genet 2016; 172 (02) 129-137
  • 13 Deardorff MA, Kaur M, Yaeger D. et al. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. Am J Hum Genet 2007; 80 (03) 485-494
  • 14 Krajewska-Walasek M, Chrzanowska K, Tylki-Szymańska A, Białecka M. A further report of Brachmann-de Lange syndrome in two sibs with normal parents. Clin Genet 1995; 47 (06) 324-327
  • 15 Wang W, Song J, Li H, Yuan H. Two de novo overlapping interstitial duplications at 10q22 associated with speech impairments, behavior problems, genital anomalies, developmental delay and İntellectual disability. Hereditary Genet 2017; 6: 2
  • 16 Chen CP, Su YN, Chern SR. et al. Prenatal diagnosis of a 4.9-Mb deletion of 10q11.21 --> q11.23 by array comparative genomic hybridization. Taiwan J Obstet Gynecol 2010; 49 (01) 117-119
  • 17 Liehr T, Schreyer I, Kuechler A. et al. Parental origin of deletions and duplications - about the necessity to check for cryptic inversions. Mol Cytogenet 2018; 11: 20
  • 18 Langley K, Martin J, Agha SS. et al. Clinical and cognitive characteristics of children with attention-deficit hyperactivity disorder, with and without copy number variants. Br J Psychiatry 2011; 199 (05) 398-403