Suzanne de Bruijn

240 Chapter 5 Table 1. Detection of the CEVA haplotype in M1 and M0 individuals Case Allele 1 Allele 2 Variant ACMG CEVA Zeroallelic SLC26A4 cases SLC014 c.2059G>T; p.(Asp687Tyr) UV3 SLC015 - - SLC017 - - SLC039 - - ACACATG-GC-C ( CEVA ) SLC043 - - SLC052 - - SLC069 - - SLC070 - - SLC073 - - SLC080 - - ACACATG-GC-C ( CEVA ) SLC084 - - SLC086 - - Monoallelic SLC26A4 cases SLC002 c.412G>T; p.(Val138Phe) UV5 SLC003 c.131dup; p.(Thr45Aspfs*42) UV5 ACACATG-GC-C ( CEVA ) SLC012 a c.707T>C; p(Leu236Pro) UV5 ACACATG-GC-C ( CEVA ) SLC013 c.1001+1G>A; p.(?) UV5 ACACATG-GC-C ( CEVA ) SLC018 c.349C>T; p.(Leu117Phe) UV5 SLC031 c.1001+1G>A; p.(?) UV5 ACACATG-GC-C ( CEVA ) SLC032 c.1334T>G; p.(Leu445Trp) UV5 SLC036 a c.1246A>C; p.(Thr416Pro) UV5 ACACATG-GC-C ( CEVA ) SLC040 a c.655_656dup; p.(Phe223Alafs*15) UV5 GTTCATG-GC-C ( V1-CEVA ) SLC045 c.1334T>G; p.(Leu445Trp) UV5 SLC048 c.706C>G; p.(Leu236Val) UV4 SLC056 c.707T>C; p(Leu236Pro) UV5 ACACATG-GC-C ( CEVA ) SLC071 a c.1334T>G; p.(Leu445Trp) UV5 GTTCATG-GC-C ( V1-CEVA ) SLC078 c.304G>C; p.(Gly102Arg) UV4 ACACATG-GC-C ( CEVA ) SLC079 c.1001+1G>A; p.(?) UV5 ACACATG-GC-C ( CEVA ) SLC085 c.706C>G; p.(Leu236Val) UV4 Presence of the CEVA haplotype was tested in zeroallelic (M0) and monoallelic (M1) SLC26A4 cases with a unilateral or bilateral enlarged vestibular aqueduct. SLC26A4 (NM_000441.1) variants reported in ClinVar as (likely) pathogenic (UV4, UV5) were considered causative, whereas variants reported as (likely) benign or of unknown significance were considered non-causative. In ten individuals, the complete CEVA haplotype was detected (ACACATG-GC-C), whereas in two individuals a shorter version of the haplotype was found, consisting of 9/12 CEVA SNPs (GTTCATG-GC-C; V1). For individuals marked with an *, it could be conclusively determined that the (V1-)CEVA haplotype is present on the trans SLC26A4 allele. ACMG, variant classification according to the American College of Medical Genetics and Genomics (ACMG) classification guidelines 51 ; UV3, uncertain significance; UV4, likely pathogenic; UV5, pathogenic.