RESUMEN
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.
Asunto(s)
Anomalías Múltiples/diagnóstico , Anomalías Congénitas/diagnóstico , Proteínas de Unión al ADN/genética , Encefalocele/diagnóstico por imagen , Mutación del Sistema de Lectura , Factores de Transcripción/genética , Anomalías Múltiples/genética , Secuencia de Aminoácidos , Niño , Anomalías Congénitas/genética , Anomalías Craneofaciales , Encefalocele/genética , Cara/anomalías , Estudios de Asociación Genética , Humanos , Masculino , Técnicas de Diagnóstico Molecular , Datos de Secuencia Molecular , Linaje , Fenotipo , Radiografía , Análisis de Secuencia de ADNRESUMEN
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.
Miscarriages result of several causes, but chromosomal anomalies are the most frequent. Thus, the cytogeneticstudies of its products and of the parents, followed by genetic counseling to involved couples, are crucialconducts. The present retrospective work aimed to investigate the karyotypes of 574 samples of miscarriageproducts, and the peripheral blood of couples involved with recurrent miscarriages in an attempt to estimatethe frequencies of chromosomal alterations. Karyotypes were previously made from the culture of chorionicvilli (miscarriages) and peripheral blood (couples), followed by the technique of G banding. It was concludedthat the observed frequency of abnormal karyotypes among miscarriage products (19.69%) and couples(7.6%) were both consistent with the literature, reinforcing the importance of cytogenetic study in thesecases.