Cornelia de Lange syndrome with <it>NIPBL</it> mutation and mosaic Turner syndrome in the same individual
<p>Abstract</p> <p>Background</p> <p>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 <it>NIPBL</it> gen...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-06-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://www.biomedcentral.com/1471-2350/13/43 |
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| author | Wierzba Jolanta Gil-Rodríguez María Polucha Anna Puisac Beatriz Arnedo María Teresa-Rodrigo María Winnicka Dorota Hegardt Fausto G Ramos Feliciano J Limon Janusz Pié Juan |
| author_facet | Wierzba Jolanta Gil-Rodríguez María Polucha Anna Puisac Beatriz Arnedo María Teresa-Rodrigo María Winnicka Dorota Hegardt Fausto G Ramos Feliciano J Limon Janusz Pié Juan |
| author_sort | Wierzba Jolanta |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>NIPBL</it> 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.</p> <p>Case presentation</p> <p>Here we report a four-year-old female with CdLS due to a frameshift mutation in the <it>NIPBL</it> 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 <it>NIPBL</it> 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 <it>NIPBL</it> mutation may have appeared before the mosaic monosomy X.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-14T03:55:31Z |
| format | Article |
| id | doaj.art-d80c8d65796c4991b635dc22793e6b46 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-14T03:55:31Z |
| publishDate | 2012-06-01 |
| publisher | BMC |
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| series | BMC Medical Genetics |
| spelling | doaj.art-d80c8d65796c4991b635dc22793e6b462022-12-21T23:18:06ZengBMCBMC Medical Genetics1471-23502012-06-011314310.1186/1471-2350-13-43Cornelia de Lange syndrome with <it>NIPBL</it> mutation and mosaic Turner syndrome in the same individualWierzba JolantaGil-Rodríguez MaríaPolucha AnnaPuisac BeatrizArnedo MaríaTeresa-Rodrigo MaríaWinnicka DorotaHegardt Fausto GRamos Feliciano JLimon JanuszPié Juan<p>Abstract</p> <p>Background</p> <p>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 <it>NIPBL</it> 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.</p> <p>Case presentation</p> <p>Here we report a four-year-old female with CdLS due to a frameshift mutation in the <it>NIPBL</it> 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 <it>NIPBL</it> 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 <it>NIPBL</it> mutation may have appeared before the mosaic monosomy X.</p> <p>Conclusions</p> <p>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.</p>http://www.biomedcentral.com/1471-2350/13/43Cornelia de Lange syndromeCdLS<it>NIPBL</it>Turner syndromeTSMonosomy X mosaicismMosaic 45,X/46,XX karyotype |
| spellingShingle | Wierzba Jolanta Gil-Rodríguez María Polucha Anna Puisac Beatriz Arnedo María Teresa-Rodrigo María Winnicka Dorota Hegardt Fausto G Ramos Feliciano J Limon Janusz Pié Juan Cornelia de Lange syndrome with <it>NIPBL</it> mutation and mosaic Turner syndrome in the same individual BMC Medical Genetics Cornelia de Lange syndrome CdLS <it>NIPBL</it> Turner syndrome TS Monosomy X mosaicism Mosaic 45,X/46,XX karyotype |
| title | Cornelia de Lange syndrome with <it>NIPBL</it> mutation and mosaic Turner syndrome in the same individual |
| title_full | Cornelia de Lange syndrome with <it>NIPBL</it> mutation and mosaic Turner syndrome in the same individual |
| title_fullStr | Cornelia de Lange syndrome with <it>NIPBL</it> mutation and mosaic Turner syndrome in the same individual |
| title_full_unstemmed | Cornelia de Lange syndrome with <it>NIPBL</it> mutation and mosaic Turner syndrome in the same individual |
| title_short | Cornelia de Lange syndrome with <it>NIPBL</it> mutation and mosaic Turner syndrome in the same individual |
| title_sort | cornelia de lange syndrome with it nipbl it mutation and mosaic turner syndrome in the same individual |
| topic | Cornelia de Lange syndrome CdLS <it>NIPBL</it> Turner syndrome TS Monosomy X mosaicism Mosaic 45,X/46,XX karyotype |
| url | http://www.biomedcentral.com/1471-2350/13/43 |
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