RESUMO
Frontonasal dysplasias (FND) comprise a spectrum of disorders caused by abnormal median facial development. Its etiology is still poorly understood but recently frontonasal dysplasia phenotypes were linked to loss-of-function mutations in the ALX homeobox gene family, which comprises the ALX1, ALX3, and ALX4 genes. All ALX-related frontonasal phenotypes till date had been compatible with an autosomal recessive mode of inheritance. In contrast, heterozygous loss-of-function mutations in ALX4 had been only associated with isolated symmetrical parietal ossification defects at the intersection of the sagittal and lambdoid sutures, known as enlarged parietal foramina. We report a family with vertical transmission from mother to son of mild frontonasal dysplasia phenotype caused by a novel ALX4 gene mutation (c.1080-1089_delGACCCGGTGCinsCTAAGATCTCAACAGAGATGGCAACT, p.Asp326fsX21).This is the first report of a frontonasal phenotype related to a heterozygous mutation in ALX4. This mutation is predicted to cause the loss of the aristaless domain in the C-terminal region of the protein and preserves the homeodomain. We speculate that a different mechanism, a dominant-negative effect, is responsible for the distinct phenotype in this family.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Congênitas/diagnóstico , Proteínas de Ligação a DNA/genética , Encefalocele/diagnóstico por imagem , Mutação da Fase de Leitura , Fatores de Transcrição/genética , Anormalidades Múltiplas/genética , Sequência de Aminoácidos , Criança , Anormalidades Congênitas/genética , Anormalidades Craniofaciais , Encefalocele/genética , Face/anormalidades , Estudos de Associação Genética , Humanos , Masculino , Técnicas de Diagnóstico Molecular , Dados de Sequência Molecular , Linhagem , Fenótipo , Radiografia , Análise de Sequência de DNARESUMO
Os abortamentos espontâneos ocorrem por diversas causas, sendo as anomalias cromossômicas do concepto,as mais freqüentes. Assim, o estudo citogenético de seus produtos e genitores, seguido do aconselhamentogenético aos casais participantes, são condutas essenciais. O presente estudo retrospectivo teve comoobjetivo investigar os cariótipos de 574 amostras de produtos de abortamentos espontâneos, bem comosangue periférico de casais com abortamentos espontâneos recorrentes, para estimar a frequência de alteraçõescromossômicas. Os cariótipos foram previamente realizados a partir da cultura de vilosidade coriônica (abortos)e sangue periférico (casais), seguida da técnica de bandeamento G. Concluiu-se que as frequências observadasde alterações cromossômicas entre os abortos (19,69%) e os casais (7,6%) foram concordantes com a literatura,reforçando a importância da análise citogenética nesses casos.
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