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Cornelia de Lange syndrome with NIPBL mutation and mosaic Turner syndrome in the same individual

Jolanta Wierzba1, María Concepción Gil-Rodríguez2, Anna Polucha3, Beatriz Puisac2, María Arnedo2, María Esperanza Teresa-Rodrigo2, Dorota Winnicka3, Fausto G Hegardt4, Feliciano J Ramos2, Janusz Limon5 and Juan Pié26*

Author Affiliations

1 Department of Pediatrics, Hematology, Oncology and Endocrinology, Department of General Nursery, Medical University of Gdańsk, Gdańsk, Poland

2 Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, and Institute of Health Sciences of Aragón, Zaragoza, Spain

3 Department of Pediatrics, Hematology and Oncology, Children University Hospital, Lublin, Poland

4 Department of Biochemistry, School of Pharmacy, University of Barcelona, and Ciber-Obn, Health Institute Carlos III, Barcelona, Spain

5 Department of Biology and Genetics, Medical University of Gdańsk, Gdańsk, Poland

6 Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology and Physiology, University of Zaragoza, Medical School, c/Domingo Miral s/n, Zaragoza, E-50009, Spain

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BMC Medical Genetics 2012, 13:43  doi:10.1186/1471-2350-13-43

Published: 7 June 2012



Cornelia de Lange syndrome (CdLS) is a dominantly inherited disorder characterized by facial dysmorphism, growth and cognitive impairment, limb malformations and multiple organ involvement. Mutations in NIPBL gene account for about 60% of patients with CdLS. This gene encodes a key regulator of the Cohesin complex, which controls sister chromatid segregation during both mitosis and meiosis. Turner syndrome (TS) results from the partial or complete absence of one of the X chromosomes, usually associated with congenital lymphedema, short stature, and gonadal dysgenesis.

Case presentation

Here we report a four-year-old female with CdLS due to a frameshift mutation in the NIPBL gene (c.1445_1448delGAGA), who also had a tissue-specific mosaic 45,X/46,XX karyotype. The patient showed a severe form of CdLS with craniofacial dysmorphism, pre- and post-natal growth delay, cardiovascular abnormalities, hirsutism and severe psychomotor retardation with behavioural problems. She also presented with minor clinical features consistent with TS, including peripheral lymphedema and webbed neck. The NIPBL mutation was present in the two tissues analysed from different embryonic origins (peripheral blood lymphocytes and oral mucosa epithelial cells). However, the percentage of cells with monosomy X was low and variable in tissues. These findings indicate that, ontogenically, the NIPBL mutation may have appeared before the mosaic monosomy X.


The coexistence in several patients of these two rare disorders raises the issue of whether there is indeed a cause-effect association. The detailed clinical descriptions indicate predominant CdLS phenotype, although additional TS manifestations may appear in adolescence.

Cornelia de Lange syndrome; CdLS; NIPBL; Turner syndrome; TS; Monosomy X mosaicism; Mosaic 45,X/46,XX karyotype