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Whole exome sequencing and array‐based molecular karyotyping as aids to prenatal diagnosis in fetuses with suspected Simpson–Golabi–Behmel syndrome
Author(s) -
Kehrer Christina,
Hoischen Alexander,
Menkhaus Ralf,
Schwab Eva,
Müller Andreas,
Kim Sarah,
Kreiß Martina,
Weitensteiner Valerie,
Hilger Alina,
Berg Christoph,
Geipel Anne,
Reutter Heiko,
Gembruch Ulrich
Publication year - 2016
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.4920
Subject(s) - exome sequencing , prenatal diagnosis , multiplex ligation dependent probe amplification , congenital diaphragmatic hernia , frameshift mutation , fetus , medicine , gene duplication , exon , genetics , mutation , biology , pregnancy , gene
Objective Simpson–Golabi–Behmel (SGBS) syndrome type 1 and type 2 represent rare X‐linked prenatal overgrowth disorders. The aim of our study is to describe the prenatal sonographic features as well as the genetic work‐up. Method Retrospective analysis of four cases with a pre‐ or postnatal diagnosis of SGBS in a single tertiary referral center within a period of 4 years. Results In the study period, four male fetuses with SGBS were detected. The final diagnosis was made prenatally in three cases. In all cases the second trimester anomaly scan revealed left sided congenital diaphragmatic hernia (CDH) with additional anomalies; three fetuses with SGBS type 1 showed fetal overgrowth. In two of these, whole exome sequencing showed a possible frameshift mutation and a point mutation in the gene GPC3 , respectively. In the third case, multiplex ligation‐dependent probe amplification (MLPA) revealed a hemizygous duplication of exon 3–7 in the gene GPC3 . In the fourth case, SGBS type 2 was confirmed by array comparative genomic hybridization (CGH) of amniotic fluid cells showing a deletion of the gene OFD1 . Conclusion We could demonstrate, that in the presence of a CDH, syndromes of the fetus can be increasingly differentiated by detailed sonography followed by a selective and graded molecular diagnostic using microarray techniques and whole exome sequencing. © 2016 John Wiley & Sons, Ltd.