RESUMO
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.
Assuntos
Anormalidades Múltiplas/genética , Acrocefalossindactilia/genética , Cromossomos Humanos Par 2/ultraestrutura , Cromossomos Humanos Par 7/ultraestrutura , Proteínas do Tecido Nervoso/deficiência , Proteínas Nucleares/deficiência , Proteína Gli2 com Dedos de Zinco/deficiência , Proteína Gli3 com Dedos de Zinco/deficiência , Adolescente , Pré-Escolar , Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 7/genética , Fissura Palatina/genética , Nanismo/genética , Feminino , Intolerância à Glucose/genética , Proteínas Hedgehog/fisiologia , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Humanos , Deficiência Intelectual/genética , Cariotipagem , Modelos Biológicos , Morfogênese/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Proteínas Nucleares/genética , Proteínas Nucleares/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Deleção de Sequência , Transdução de Sinais/genética , Síndrome , Proteína Gli2 com Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/fisiologia , Proteína Gli3 com Dedos de Zinco/genética , Proteína Gli3 com Dedos de Zinco/fisiologiaRESUMO
Less than 1% of the cases with Angelman syndrome (AS) are caused by chromosomal rearrangements. This category of AS is not well defined and may manifest atypical phenotypes. Here, we report a girl with AS due to der(13)t(13;15)(q14.1;q12)mat. SNP array detected the precise deletion/duplication points and the parental origin of the 15q deletion. Multicolor FISH confirmed a balanced translocation t(13;15)(q14.1;q12) in her mother. Her facial appearance showed some features of dup(13)(pterâq14). Also, she lacked the most characteristic and unique behavioral symptoms of AS, i.e., frequent laughter, happy demeanor, and easy excitability. A review of the literature indicated that AS cases caused by chromosomal rearrangements can be classified into 2 major categories and 4 groups. The first category is paternal uniparental disomy 15, which is subdivided into isodisomy by de novo rob(15;15) and heterodisomy caused by paternal translocation. The second category is the deletion of the AS locus due to maternal reciprocal translocation, which is subdivided into 2 groups associated with partial monosomy by 3:1 segregation and partial trisomy by adjacent-2 segregation. Classification into these categories facilitates the understanding of the mechanisms of chromosomal rearrangements and helps in accurate diagnosis and genetic counseling of these rare forms of AS.