Supplementary Material for: Congenital Adrenal Hyperplasia, Ovarian Failure and Ehlers-Danlos Syndrome due to a 6p Deletion

Cryptic deletions in balanced de novo translocations represent a frequent cause of abnormal phenotypes, including Mendelian diseases. In this study, we describe a patient with multiple congenital abnormalities, such as late-onset congenital adrenal hyperplasia (CAH), primary ovarian failure and Ehlers-Danlos syndrome (EDS), who carries a de novo t(6;14)(p21;q32) translocation. Genomic array analysis identified a cryptic 1.1-Mb heterozygous deletion, adjacent to the breakpoint on chromosome 6, extending from 6p21.33 to 6p21.32 and affecting 85 genes, including <i>CYP21A2,</i><i>TNXB</i> and <i>MSH5</i>. Multiplex ligation-dependent probe amplification analysis of the 6p21.3 region was performed in the patient and her family and revealed a 30-kb deletion in the patient's normal chromosome 6, inherited from her mother, resulting in homozygous loss of genes <i>CYP21A1P</i> and <i>C4B</i>. <i>CYP21A2 </i>sequencing showed that its promoter region was not affected by the 30-kb deletion, suggesting that the deletion of other regulatory sequences in the normal chromosome 6 caused a loss of function of the <i>CYP21A2</i> gene. EDS and primary ovarian failure phenotypes could be explained by the loss of genes <i>TNXB</i> and <i>MSH5</i>, a finding that may contribute to the characterization of disease-causing genes. The detection of this de novo microdeletion drastically reduced the estimated recurrence risk for CAH in the family.