Suzanne de Bruijn

104 Chapter 3.1 isoforms ( Figure S2 ). RIPOR2 has previously been associated with recessively inherited early-onset hearing loss and is positioned 0.9 Mb centromeric of the DFNA21 locus. 10,11 No copy number variants were detected that were shared by all three subjects. W97-056 48 21 26 20 50 52 37 50 43 36 7 29 ? ? 26 24 40 35 30 17 32 27 30 8 8 5 23 43 70 14 46 ? 20 33 47 34 51 47 ? 42 38 30 12 12 8 M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ M/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ 44 +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ +/+ 1 2 1 2a 2 10 10a 11 11a 12a 12 13 14a 14 15 15a 16 17 18a 18 39 38 35 34 33 32 29 28 27 26 25 24 23 22 21 20 20a 2 1 19 20a 20 3 3a 4 4a 5 5a 32 31 30 29 28 27 26a 26 25 24 23 22a 22 21a 21 40 41 42 43 44 45 46 50 51 I III IV V II III IV II Figure 1. Pedigree of family W97-056 and segregation of RIPOR2 variant c.1696_1707del. For affected and unaffected family members, the age of onset of hearing loss or the age at the most recent audiometric evaluation are indicated in the pedigree symbols, respectively. Subjects who did not report an age of onset are indicated with a question mark. The index case is marked by an arrow. Exome sequencing was performed in subjects with an underlined genotype. Subjects determined to be affected by heteroanamnesis are indicated with a vertical black bar. The subject marked in grey is diagnosed with intellectual disability and excluded from further participation in this study. Subject identifiers correspond to those in de Brouwer et al., 2005. 10 M, c.1696_1707del; +, wildtype. Segregation analysis identified the RIPOR2 variant in 20 of 23 affected subjects of family W97-056 ( Figure 1 ). The variant was not found in subjects III:14, III:20, and III:21; a recombination event in subject III:14 previously delimited the centromeric border of the DFNA21 locus. 10 The RIPOR2 c.1696_1707del variant was also found in three unaffected familymembers (V:2, age 23 years; IV:26, age 40 years and III:28, age 51 years). The strong association of the RIPOR2 variant with HL in this family urged us to further address this and other variants in RIPOR2 in families with (adult-onset) HL.