Table 2.
Ultrarare variants of DFNA genes in mARHL cases
| Patient (x) | Gene/protein | Deafness form | Protein activity or function/location | Variants |
| 33029 (3) | CDHR23/cadherin-related 23 | DFNB12/DFNA†/ARSD:USH1D | Ca2+-dependent cell adhesion, component of the MET machinery/IHCs, OHCs | c.5131G > A; p.(Val1711Ile) |
| c.9932C > T; p.(Ser3311Leu) | ||||
| PAR132 | COL11A1/collagen type XI α1-chain | DFNA37/ARSD: STL2 | Extracellular matrix component/tectorial membrane, inner sulcus, Claudius' cells, Boettcher’s cells | c.5401G > T; p.(Gly1801Cys) |
| PAR136 | DIAPH1/protein diaphanous homolog 1 | DFNA1 | Actin nucleation and elongation factor/IHCs and OHCs, inner and outer pillar hair cells, spiral ganglion neurons | c.3128A > G; p.(His1043Arg) |
| PAR089 | ESPN/espin | DFNA/DFNB36 | Multifunctional actin-bundling protein/IHCs, OHCs | c.2515C > A; p.(Pro839Thr) |
| PAR057 | EYA4/eyes absent homolog 4 | DFNA10 | Transcriptional coactivator/cochlear sensory epithelia | c.(84-20_146)_(*2410_?)del |
| PAR032 (3) | GRHL2/grainyhead-like 2 | DFNA28 | Transcription factor/IHCs, OHCs, supporting cells, spiral ganglion neurons | c.931_932del; p.(Asp311*) |
| PAR016 (4) | KCNQ4/voltage-gated K+ channel subfamily KQT member 4 | DFNA2 | K+ channel plasma membrane/OHCs | c.1012C > G; p.(Arg338Gly) |
| PAR047 | c.1316G > A; p.(Arg439His) | |||
| PAR007 (2) | MITF/microphthalmia-associated transcription factor | ADSD:WS2 | Transcription factor/IHCs, OHCs | c.666 + 1G > T |
| 33016 (2) | MYH14/myosin-14 | DFNA4 | Actin-based motor protein/IHCs, OHCs, and the SV, cells lining the cochlear duct (Hensen and Claudius’ cells, external sulcus cells, and spiral prominence epithelial cells) | c.3745G > A; p.(Glu1249Lys) |
| PAR062 | MYO6/unconventional myosin-VI | DFNA22/DFNB37 | Actin-based motor protein/IHCs, OHCs | c.866_869del; p.(Lys289Argfs*17) |
| PAR013 (2) | c.1465C > G; p.(Leu489Val) | |||
| 33006 (2) | c.1926C > A; p.(Ser642Arg) | |||
| PAR010 | c.3791del; p.(Asn1264Metfs*21) | |||
| PAR023 | MYO7A/unconventional myosin-VIIa | DFNA11/DNFB2/ARSD:USH1B | Actin-based motor protein/IHCs, OHCs | c.3750 + 5G > T |
| 33008 | c.3956T > C; p.(Val1319Ala) | |||
| PAR051 | OSBPL2/oxysterol-binding protein-related protein 2 | DFNA67 | Intracellular lipid-binding receptor/IHCs, OHCs, SV, spiral ganglion neurons, and spiral ligament | c.337C > G; p.(His113Asp) |
| PAR031 (2) | PTPRQ/protein tyrosine phosphatase receptor type Q | DFNA73/DFNB84 | Plasma membrane tyrosine phosphatase receptor/IHC and OHC hair bundles | c.1148G > A; p.(Gly383Glu) |
| PAR125 | c.2521C > T; p.(Arg841Trp) | |||
| PAR126 (2) | SCD5/stearoyl-CoA desaturase 5 | DFNA | Integral membrane protein of the ER, catalyzes the formation of monounsaturated fatty acids from saturated fatty acids/IHCs, OHCs, SV, spiral ganglion neurons | c.680G > A; p.(Arg227His) |
| 33002 | TECTA/α-tectorin | DFNA8/12/DFNB21 | Extracellular matrix component/tectorial membrane | c.1376G > T; p.(Gly459Val) |
| PAR070 (2) | c.1951G > A; p.(Gly651Ser) | |||
| PAR054 (2) | c.2670_2671del; p.(Asp891Profs*8) | |||
| PAR079 | TJP2/tight junction protein ZO-2 | DFNA51 | Subplasma membrane protein of tight and adherens junctions/hair cell-supporting cell junctions | c.2428G > A; p.(Val810Met) |
| PAR093 (2) | TMC1/TM channel-like protein 1 | DFNA36/DFNB7/11 | Plasma membrane TM protein, component of the MET channel/IHCs and OHCs | c.980A > T; p.(Asn327Ile) |
| PAR094 | TRRAP/trafficking protein particle complex | DFNA75 | Adapter protein in chromatin complexes/spiral ligament | c.2086C > T; p.(Arg696Cys) |
| PAR009 (2) | WFS1/wolframin | DFNA6/14/38/ARSD:WFS1 | TM protein of the ER; putative ion channel; Ca2+ signaling and ER stress pathways/IHCs, OHCs spiral ganglion neurons | c.2150dup; p.(Ser718Valfs*41) |
x is the number of ARHL-affected individuals studied in each family. CoA, coenzyme A; ER, endoplasmic reticulum; IHC, inner hair cell; STL, Stickler syndrome; SV, stria vascularis; USH, Usher syndrome; WFS1, Wolfram syndrome; WS, Waardenburg syndrome.