Figure 1.

Clinical and molecular characterization of the case. (A) Frontal and lateral view of the proband at the age of 36 months. Note the mild frontal bossing, low-set posteriorly rotated ears, and thin lips. Earing aids are in place. The patient also displays brachydactyly of both hands and feet and clinodactily of V finger of hands. Other clinical findings are listed in the side table, where 3 out of 6 NH-CSS for SRS are in bold characters. (B) The LR-PCR amplicons of the patient (P) and both her father (F) and mother (M) were resolved on a 0.8% agarose gel. The patient (P) displayed a unique shorter band of about 2.5 kb in size, the father (F) showed a unique band of over 10 kb in size, corresponding to the expected 14.7 kb wild type band, whereas her mother (M) showed two bands corresponding to the wild type and the deleted alleles. MW, molecular weight. (C) The proximal and distal breakpoints of the SLC26A4 intragenic deletion were mapped within SLC26A4 IVS16 and the IVS20, respectively. The deletion is about 13 kb long. Sequence alignments of the junction fragments revealed an insertion of a part of CCDC126 IVS3. The rejoining between SLC26A4 IVS20 and CCDC126 IVS3 distal bkp occurred through a de novo 3 bp GCC insertion. (D) Sequencing of the RT-PCR amplicons, extending from exons 13–14 to 3′UTR of SLC26A4, confirmed the homozygous deletion of exons 17–20 in the child (P). The father (F) showed only the long transcript corresponding to the wild type pendrin, whereas the mother (M) displayed a short transcript and a long one, consistent with a heterozygous state of the deletion. MW, molecular weight.