Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation

Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or X-linked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskelet...

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Detalles Bibliográficos
Autores: Baquero Montoya, Carolina, Gil Rodríguez, María Concepción, Hernández Marcos, María, Teresa Rodrigo, María Esperanza, Vicente Gabas, Alicia, Bernal, María Luisa, Casale, Cesar Horacio, Bueno Lozano, Gloria, Bueno Martínez, Inés, Queralt, Ethel, Villa, Olaya, Hernando Davalillo, Cristina, Armengol, Lluís, Gómez Puertas, Paulino, Puisac, Beatriz, Selicorni, Angelo, Ramos, Feliciano J., Pié, Juan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/180663
Acceso en línea:http://hdl.handle.net/11336/180663
Access Level:acceso abierto
Palabra clave:BHLHA9 DUPLICATION
CDLS
CORNELIA DE LANGE SYNDROME
EXOME SEQUENCING
HEAT REPEAT
IPSILATERAL
MUSCULOSKELETAL INVOLVEMENT
NIPBL MUTATION
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario:Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or X-linked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.

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