Whole exome sequencing confirms the clinical diagnosis of Marfan syndrome combined with X-linked hypophosphatemiaReportar como inadecuado

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Journal of Translational Medicine

, 13:179

First Online: 04 June 2015Received: 07 February 2015Accepted: 13 May 2015DOI: 10.1186-s12967-015-0534-9

Cite this article as: Sheng, X., Chen, X., Lei, B. et al. J Transl Med 2015 13: 179. doi:10.1186-s12967-015-0534-9


BackgroundTo determine the genetic lesions and to modify the clinical diagnosis for a Chinese family with significant intrafamilial phenotypic diversities and unusual presentations.

MethodsThree affected patients and the asymptomatic father were included and received comprehensive systemic examinations. Whole exome sequencing WES was performed for mutation detection. Structural modeling test was applied to analyze the potential structural changes caused by the missense substitution.

ResultsThe proband showed a wide spectrum of systemic anomalies, including bilateral ectopia lentis, atrial septal defect, ventricular septal defect, widening of tibial metaphysis with medial bowing, and dolichostenomelia in digits, while her mother and elder brother only demonstrated similar skeletal changes. A recurrent mutation, PHEX p.R291*, was found in all patients, while a de novo mutation, FBN1 p.C792F, was only detected in the proband. The FBN1 substitution was also predicted to cause significant conformational change in fibrillin-1 protein, thus changing its physical and biological properties.

ConclusionsTaken together, we finalized the diagnosis for this family as X-linked hypophosphatemia XLH, and diagnosed this girl as Marfan syndrome combined with XLH, and congenital heart disease. Our study also emphasizes the importance of WES in assisting the clinical diagnosis for complicated cases when the original diagnoses are challenged.

Xunlun Sheng, Xue Chen and Bo Lei are contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-015-0534-9 contains supplementary material, which is available to authorized users.

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Autor: Xunlun Sheng - Xue Chen - Bo Lei - Rui Chen - Hui Wang - Fangxia Zhang - Weining Rong - Ruoshui Ha - Yani Liu - Feng Zha

Fuente: https://link.springer.com/

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