Whole exome sequencing confirms the clinical diagnosis of Marfan syndrome combined with X-linked hypophosphatemia.

TitleWhole exome sequencing confirms the clinical diagnosis of Marfan syndrome combined with X-linked hypophosphatemia.
Publication TypeJournal Article
Year of Publication2015
AuthorsSheng, X, Chen, X, Lei, B, Chen, R, Wang, H, Zhang, F, Rong, W, Ha, R, Liu, Y, Zhao, F, Yang, P, Zhao, C
JournalJ Transl Med
Volume13
Pagination179
Date Published2015 Jun 04
ISSN1479-5876
KeywordsAdult, Amino Acid Sequence, Base Sequence, Child, Exome, Familial Hypophosphatemic Rickets, Family, Female, Humans, Male, Marfan Syndrome, Microfilament Proteins, Molecular Sequence Data, Mutation, Pedigree, PHEX Phosphate Regulating Neutral Endopeptidase, Reproducibility of Results, Sequence Analysis, DNA
Abstract

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

METHODS: Three 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.

RESULTS: The 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.

CONCLUSIONS: Taken 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.

DOI10.1186/s12967-015-0534-9
Alternate JournalJ Transl Med
PubMed ID26040324
PubMed Central IDPMC4455986