PRENATAL DIAGNOSIS OF ROBERTS SYNDROME AND DETECTION OF AN ESCO2 FRAMESHIFT MUTATION IN A PAKISTANI FAMILY

Authors: Solveig Schulz1*, Claudia Gerloff2, Susanne Ledig1, Dorothea Langer3, Mariannne Volleth1,
Katayoon Shirneshan1 and Peter Wieacker1,4

Objectives We report two siblings with Roberts syndrome (RBS), and an attempt to delineate the underlying
molecular mechanism leading to familial recurrence.

Methods Cytogenetic studies and direct sequencing of the ESCO2 gene were carried out in the second
affected fetus and the parents. Fetal DNA was obtained from amniocytes after amniocentesis. Parental DNA
was obtained from peripheral blood samples.

Results Cytogenetic analysis of amniocytes revealed a normal male karyotype in 20 analyzed metaphases and
chromosomal aneuploidies in 10 metaphases. All metaphases displayed premature separation of centromeres
and puffing of heterochromatic regions near the centromere. A homozygous mutation leading to a frameshift in
ESCO2 was identified in the fetal DNA sample. Both parents are heterozygous carriers of the same mutation.

Conclusion The present case demonstrates the prenatal diagnosis of RBS associated with a frameshift
mutation in ESCO2. Copyright  2008 John Wiley & Sons, Ltd.