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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
Joanna Goes Castro Meira
1   Department of Medical Genetics, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil
,
Manoel Alfredo Curvelo Sarno
2   Maternidade Climério de Oliveira, Universidade Federal da Bahia, Salvador, BA, Brazil
,
Ágatha Cristhina Oliveira Faria
3   Center 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
3   Center 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
3   Center 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
1   Department of Medical Genetics, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil
,
Dione Fernandes Tavares
1   Department of Medical Genetics, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil
,
Angelina Xavier Acosta
1   Department of Medical Genetics, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil
› Author Affiliations
Further Information

Publication History

14 December 2017

13 June 2018

Publication Date:
19 September 2018 (online)

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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
 

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