TY - JOUR
T1 - Diaphanospondylodysostosis
T2 - Refining the prenatal diagnosis of a rare skeletal disorder
AU - Greenbaum, Lior
AU - Gilboa, Yinon
AU - Raas-Rothschild, Annick
AU - Barel, Ortal
AU - Kol, Nitzan
AU - Reznik-Wolf, Haike
AU - Pode-Shakked, Ben
AU - Finezilber, Yael
AU - Messing, Baruch
AU - Berkenstadt, Michal
N1 - Publisher Copyright:
© 2018 Elsevier Masson SAS
PY - 2019/3
Y1 - 2019/3
N2 - Diaphanospondylodysostosis (DSD) is a rare autosomal recessive skeletal disorder, characterized mainly by ossification defects in vertebrae, thorax malformations, renal cystic dysplasia and usually death in the perinatal period. DSD is caused by mutations in the bone morphogenetic protein-binding endothelial regulator (BMPER) gene. We describe the prenatal findings of a non-consanguineous Jewish couple (shared Balkan origin), with three affected fetuses that presented with malformations in the spine and chest, reduced ossification of the skull and spine, horseshoe kidney and increased nuchal translucency. The unique combination of these ultrasound (US) features raised the possibility of DSD, which was confirmed by whole exome sequencing (WES) performed on a single fetal DNA and familial segregation. In the three fetuses, a novel homozygous mutation in BMPER (c.410T > A; p.Val137Asp) was found. This mutation, which segregated in the family, was not found in 65 controls of Jewish Balkan origin, and in several large databases. Taken together, the combination of a detailed prenatal US examination and WES may be highly effective in confirming the diagnosis of a rare genetic disease, in this case DSD.
AB - Diaphanospondylodysostosis (DSD) is a rare autosomal recessive skeletal disorder, characterized mainly by ossification defects in vertebrae, thorax malformations, renal cystic dysplasia and usually death in the perinatal period. DSD is caused by mutations in the bone morphogenetic protein-binding endothelial regulator (BMPER) gene. We describe the prenatal findings of a non-consanguineous Jewish couple (shared Balkan origin), with three affected fetuses that presented with malformations in the spine and chest, reduced ossification of the skull and spine, horseshoe kidney and increased nuchal translucency. The unique combination of these ultrasound (US) features raised the possibility of DSD, which was confirmed by whole exome sequencing (WES) performed on a single fetal DNA and familial segregation. In the three fetuses, a novel homozygous mutation in BMPER (c.410T > A; p.Val137Asp) was found. This mutation, which segregated in the family, was not found in 65 controls of Jewish Balkan origin, and in several large databases. Taken together, the combination of a detailed prenatal US examination and WES may be highly effective in confirming the diagnosis of a rare genetic disease, in this case DSD.
KW - BMPER
KW - Diaphanospondylodysostosis
KW - Ischiospinal dysostosis
KW - Skeletal dysplasia
UR - http://www.scopus.com/inward/record.url?scp=85050583357&partnerID=8YFLogxK
U2 - 10.1016/j.ejmg.2018.07.004
DO - 10.1016/j.ejmg.2018.07.004
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C2 - 30006055
AN - SCOPUS:85050583357
SN - 1769-7212
VL - 62
SP - 167
EP - 171
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 3
ER -