Diagnosis of Atelosteogenesis Type I suggested by Fetal Ultrasonography and Atypical Paternal Phenotype with Mosaicism

Joanna Goes Castro Meira; Manoel Alfredo Curvelo Sarno; Ágatha Cristhina Oliveira Faria; Guilherme Lopes Yamamoto; Débora Romeo Bertola; Gabriela Gayer Scheibler; Dione Fernandes Tavares; Angelina Xavier Acosta

doi:10.1055/s-0038-1670684

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics, Inhaltsverzeichnis

CC BY 4.0 · Rev Bras Ginecol Obstet 2018; 40(09): 570-576
DOI: 10.1055/s-0038-1670684

Case Report

Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Diagnosis of Atelosteogenesis Type I suggested by Fetal Ultrasonography and Atypical Paternal Phenotype with Mosaicism

Diagnóstico de atelosteogênese tipo I sugerido por ultrassonografia fetal e fenótipo paterno atípico com mosaicismo

Authors

Joanna Goes Castro Meira

¹Department of Medical Genetics, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil
Manoel Alfredo Curvelo Sarno

²Maternidade Climério de Oliveira, Universidade Federal da Bahia, Salvador, BA, Brazil
Ágatha Cristhina Oliveira Faria

³Center for Studies of the Human Genome and of Stem Cells Department of Genetics and Evolutionary Biology, Institute of Biosciences, Universidade de São Paulo, São Paulo, SP, Brazil
Guilherme Lopes Yamamoto

³Center for Studies of the Human Genome and of Stem Cells Department of Genetics and Evolutionary Biology, Institute of Biosciences, Universidade de São Paulo, São Paulo, SP, Brazil
Débora Romeo Bertola

³Center for Studies of the Human Genome and of Stem Cells Department of Genetics and Evolutionary Biology, Institute of Biosciences, Universidade de São Paulo, São Paulo, SP, Brazil
Gabriela Gayer Scheibler

¹Department of Medical Genetics, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil
Dione Fernandes Tavares

¹Department of Medical Genetics, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil
Angelina Xavier Acosta

¹Department of Medical Genetics, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil

Abstract

Atelosteogenesis type I (AOI) is an autosomal dominant skeletal dysplasia caused by mutations in the filamin B (FLNB) gene with classic and well-recognizable clinical findings. However, parents affected with a mild phenotype, probably with somatic mosaicism, can generate offspring with a much more severe phenotype of AOI. In the present report, we describe a female newborn with classic AOI leading to early neonatal death, whose diagnostic was based on prenatal radiological findings and on the physical examination of the father. Since her father had limb deformities and corporal asymmetry, suggesting somatic mosaicism, his biological samples were analyzed through a gene panel for skeletal dysplasias. A missense mutation not previously described in the literature was detected in the FLNB gene, affecting ∼ 20% of the evaluated cells and, therefore, confirming the diagnosis of mosaic AOI in the father. The molecular analysis of the father was crucial to suggest the diagnosis of AOI in the newborn, since she died early and there were no biological samples available.

Resumo

A atelosteogênese tipo I (AOI) é uma displasia esquelética autossômica dominante causada por mutações no gene filamina B (FLNB) com achados clínicos clássicos e bem reconhecíveis. No entanto, pais afetados com um fenótipo mais leve, provavelmente com mosaicismo somático, podem gerar uma prole com um fenótipo muito mais grave de AOI. No presente relato, descrevemos um recém-nascido do sexo feminino com AOI clássica, que levou à morte neonatal precoce, e cujo diagnóstico foi baseado em achados radiológicos pré-natais e no exame físico de seu genitor. Como o genitor apresentava deformidades em membros e assimetria corporal, que sugeriam mosaicismo somático, suas amostras biológicas foram analisadas por meio de um painel de genes para displasias esqueléticas. Uma mutação missense, não descrita anteriormente na literatura, foi detectada no gene FLNB, afetando ∼ 20% das células avaliadas, e, portanto, confirmando o diagnóstico de AOI em mosaico no genitor. A análise molecular realizada no genitor foi fundamental para sugerir o diagnóstico de AOI na recém-nascida, uma vez que esta morreu precocemente, e não havia amostras biológicas disponíveis.

Keywords

atelosteogenesis - somatic mosaicism - skeletal dysplasia - FLNB - exome-target sequencing - fetal ultrasonography

Palavras-chave

atelosteogênese - mosaicismo somático - displasia esquelética - FLNB - sequenciamento do exoma - ultrassonografia fetal

Volltext

Referenzen

References
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