Genetic testing has the potential to impact hearing preservation following cochlear implantation

Figures & data

Table 1. Characteristics of patients evaluated in this study (N = 44).

Characteristic	Number
Sex
Male	20
Female	24
Inheritance
Autosomal recessive	7
Autosomal dominant or mitochondrial	12
Sporadic	20
Ambiguous	2
Total	41^a
Implanted ear
Right	27
Left	23
Total	50^b
Inserted cochlear implant device
FLEX^soft	6
FLEX^28	17
FLEX^24	27
Total	50^b
	Mean ± SD
Age at cochlear implantation in years	36.4 ± 18.1
Preoperative LFA^c (dB)	48.7 ± 18.3

^aTwo affected patients in three families each.

^bSix patients received bilateral EAS.

^cLFA: average low-frequency hearing thresholds at 125, 250, and 500 Hz.

Figure 1. Etiology of patients with residual acoustic hearing. Orange indicates genetic causes of hearing loss; yellow, other causes; grey, unknown (n = 41).

Table 2. Summary of the clinical features and information of the variants identified as likely causative in this study.

Family			Implant				CADD	ACMG		Pre-op	6M post-activation	HP numerical
No.	Sample ID	Gender	age (years)	Gene	HGVS variant	Zygosity	Phred	Criteria	Implant	LFA (dB)	LFA (dB)	scale (%)
1-I^a	SNS5117	Female	45	CDH23	NM_022124: c.4762C > T, p.R1588W	hom	26.6	VUS	FLEX24	45.0	55.0	79.3
			48						FLEX24	60.0	71.7	65.0
1-II^a	SNS5121	Male	53	CDH23	NM_022124: c.4762C > T, p.R1588W	hom	26.6	VUS	FLEX28	55	50	95.3
2	SNS1169	Female	38	TMPRSS3	NM_032404: c.607C > T, p.Q203X	het	35	Pathogenic	FLEX24	36.7	61.7	55.9
			39		NM_032404: c.778G > A, p.A260T	het	28.9	Pathogenic	FLEX24	80.0	90.0	0.0
3-I^a	2885	Male	12	CDH23	NM_022124: c.719C > T, p.P240L	het	25.8	Pathogenic	FLEXsoft	73.3	73.3	92.3
					NM_022124: c.902C > T, p.R301Q	het	34	Likely pathogenic
3-II^a	2886	Male	12	CDH23	NM_022124: c.719C > T, p.P240L	het	25.8	Pathogenic	FLEXsoft	80.0	81.7	100.0
					NM_022124: c.902C > T, p.R301Q	het	34	Likely pathogenic	–	–	–	–
4	SNS5142	Female	70	MYO15A	NM_016239: c.10263C > G, p.I3412M	hom	23.1	Likely pathogenic	FLEX24	70.0	85.0	15.0
5	SNS5791	Male	29	ACTG1	NM_001614: c.914T > C, p.M305T	het	24.2	VUS	FLEX24	35.0	75.0	22.4
6	SNS0417	Male	39	ACTG1	NM_001614: c.895C > G, p.L299V	het	20	VUS	FLEX24	43.3	53.3	61.5
7	SNS5792	Female	52	CDH23	NM_022124: c.719C > T, p.P240L	het	25.8	Pathogenic	FLEX24	28.3	36.7	90.9
					NM_022124: c.6085C > T, p.R2029W	het	16.8	Pathogenic	–	–	–	–
8	SNS5355	Male	45	TMPRSS3	NM_032404: c.647G > T, p.W216L	het	34	VUS	FLEX24	25.0	45.0	68.1
					NM_032404: c.771G > T, p.H257Q	het	28	VUS	–	–	–	–
9-I^a	HL0186	Female	12	SLC26A4	NM_000441: c.1229C > T, p.T410M	hom	33	Pathogenic	FLEX28	63.3	70.0	70.8
9-II^a	SNS5626	Female	9	SLC26A4	NM_000441: c.1229C > T, p.T410M	hom	33	Pathogenic	FLEX28	50.0	65.0	62.5
10	HL0036	Female	28	MYO7A	NM_000260: c.0652G > A, p.D218N	het	27.4	Likely pathogenic	FLEXsoft	66.7	71.7	75.0
11	AG6121	Female	34	CLDN14	NM_144492: c.241C > T, p.R81C	hom	27.6	VUS	FLEX28	68.3	81.7	81.3
12	SNS5967	Male	50	CDH23	NM_022124: c.2866C > T, p.E956K	het	34	Pathogenic	FLEX28	50.0	56.7	78.6
					NM_022124: c.4762C > T, p.R1588W	het	26.6	VUS	–	–	–	–
13	AG5940	Male	13	SLC26A4	NM_000441: c.919-2A > G	het	24.8	Pathogenic	FLEX28	78.3	81.7	100.0
					NM_000441: c.1229C > T, p.T410M	het	33	Pathogenic	–	–	–	–
14	AL6787	Male	21	LOXHD1	NM_144612: c.4212 + 1G > A	het	Unknown	Pathogenic	FLEX28	33.3	66.7	37.2
					NM_144612: c.6168delC	het	24.2	Pathogenic	–	–	–	–
15	HL2709	Female	10	MYO7A	NM_000260: c.4477G > A, p.V1493I	het	24.5	VUS	FLEX24	18.3	15.0	100.0
16	HL0501	Male	8	MYO15A	NM_016239: c.535G > T, p.E179X	het	36	Pathogenic	FLEX24	35.0	33.3	100.0
					NM_016239: c.9413T > A, p.L3138Q	het	24.4	Likely pathogenic	–	–	–	–
17	2729259	Female	14	CDH23	NM_022124: c.719C > T, p.P240L	het	25.8	Pathogenic	FLEX28	56.7	48.3	100.0
					NM_022124: c.2866C > T, p.E956K	het	34	Pathogenic	–	–	–	–

^aTwo affected patients in three families each.

Table 3. Univariate analysis of variables and hearing preservation scale.

Variable	Pearson’s R square	p Value
Age	0.186	.001
Pre-operative LFA^a	0.013	.404
CDL^b	0.0004	.885

^aLFA: average low-frequency hearing thresholds at 125, 250, and 500 Hz.

^bCDL: cochlear duct length measured by OTOPLAN.

Figure 2. Comparison of hearing threshold shifts after implant surgery. Median, interquartile, minimum and maximum scores for the HP scale. Statistical analysis by one-way ANOVA with Bonferroni’s correction. NS: statistically not significant.

Figure 3. Comparison of HP scores among three types of CI electrode array. Median, interquartile, minimum and maximum scores for the HP scale. Statistical analysis by one-way ANOVA with Bonferroni’s correction. NS: statistically not significant.

Figure 4. Average pre- (blue line) and post-operative (red line) air conduction hearing thresholds for patients with (A) pathogenic variants in the CDH23, MYO7A, or MYO15A gene, and (B) hearing loss due to other causes. Error bars represent the SD. (C) A comparison of HP scores in each group. Median, interquartile, minimum and maximum scores for the HP scale. Statistical analysis by Mann–Whitney test.