Reduction of Cellular Expression Levels Is a Common Feature of Functionally Affected Pendrin (SLC26A4) Protein Variants

Table 2 Functional and molecular features of pendrin variants identified patients without (group I) and with (group II) EVA.^a

Group	Patient ID	Protein variants: Allele 1 Allele 2	Function: Allele 1 Allele 2	Localization: Allele 1 Allele 2	Expression: Allele 1 Allele 2	Pendrin-related deafness	Reference: Allele 1 Allele 2
I	C15	p.V138F	Lost	ER	_?	Probably not	(44)
		WT	WT	PM	WT		—
	C26^b	p.C282Y	Reduced (41%)	PM	Reduced	Probably not	Present work
		WT	WT	PM	WT		—
	C01	p.V609G	Reduced (45%)	?	?	Probably not	(45)
		WT	WT	PM	WT		—
	C04	p.V609G	Reduced (45%)	_?	_?	Probably not	(45)
		WT	WT	PM	WT		—
	C09	p.V609G	Reduced (45%)	?	?	Probably not	(45)
		WT	WT	PM	WT		—
II	21	p.P142L	Reduced (76%)	PM	Reduced	Yes	Present work
		p.S93Rfs3*	Lost	?	?		(46)
	16	p.G149R	Reduced (55%)	PM/ER	Reduced	_?	Present work
		WT	WT	PM	WT		—
	18	p.T193I	Lost	ER	Greatly reduced	?	Present work
		WT	WT	PM	WT		—
	22	p.R409H	Lost or reduced (33%)	PM/ER	Reduced	Yes	(47) and data not shown
		p.R409H	Lost or reduced (33%)	PM/ER	Reduced		(47) and data not shown
	02	p.T410M	Lost	ER	_?	yes	(44)
		SS (c.1707+5G>A)	Most likely lost	—	Lost		(27)
	06	p.Q413R	Reduced (60%)	ER	Reduced	Yes	Present work
		p.V138F	Lost	ER	?		(44)
	23	L445W	Lost	ER	Greatly reduced	Yes	Present work
		SS (c.1001 + 1G>A)	Most likely lost	?			(26)
	L1^b	p.V609G	Reduced (45%)	_?	_?	_?	(45)
		WT	WT	PM	WT		—
	15	p.R776C	Unaffected	PM	Unaffected	No	Present work
		WT	WT	PM	WT		—

^aThe magnitude of reduction in pendrin transport activity is indicated in %. Question mark (?) denotes an undetermined feature. SS, splicing site variant; *, stop codon.
^bMonoallelic mutation (c.35delG) in the connexin GJB2 gene was detected in the same patient.

ISSN: 1528-3658