Human Malformation Syndromes of Defective GLI: Opposite Phenotypes of 2q14.2 (GLI2) and 7p14.2 (GLI3) Microdeletions and a GLIA/R Balance Model.
Cytogenet Genome Res
; 153(2): 56-65, 2017.
Article
em En
| MEDLINE
| ID: mdl-29298444
ABSTRACT
GLI family zinc finger proteins are transcriptional effectors of the sonic hedgehog signaling pathway. GLI regulates gene expression and repression at various phases of embryonic morphogenesis. In humans, 4 GLI genes are known, and GLI2 (2q14.2) and GLI3 (7p14.1) mutations cause different syndromes. Here, we present 2 distinctive cases with a chromosomal microdeletion in one of these genes. Patient 1 is a 14-year-old girl with Culler-Jones syndrome. She manifested short stature, cleft palate, and mild intellectual/social disability caused by a 6.6-Mb deletion of 2q14.1q14.3. Patient 2 is a 2-year-old girl with Greig cephalopolysyndactyly contiguous gene deletion syndrome. She manifested macrocephaly, preaxial polysyndactyly, psychomotor developmental delay, cerebral cavernous malformations, and glucose intolerance due to a 6.2-Mb deletion of 7p14.1p12.3 which included GLI3, GCK, and CCM2. Each patient manifests a different phenotype which is associated with different functions of each GLI gene and different effects of the chromosomal contiguous gene deletion. We summarize the phenotypic extent of GLI2/3 syndromes in the literature and determine that these 2 syndromes manifest opposite features to a certain extent, such as midface hypoplasia or macrocephaly, and anterior or posterior side of polydactyly. We propose a GLIA/R balance model that may explain these findings.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Anormalidades Múltiplas
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Acrocefalossindactilia
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Cromossomos Humanos Par 2
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Cromossomos Humanos Par 7
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Proteínas Nucleares
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Proteína Gli3 com Dedos de Zinco
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Proteína Gli2 com Dedos de Zinco
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Child, preschool
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Female
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Humans
Idioma:
En
Revista:
Cytogenet Genome Res
Assunto da revista:
GENETICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão