Monogenic hearing loss

Gene: SOX2

I don't know

The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.

Created: 5 Dec 2024, 8:33 p.m. | Last Modified: 5 Dec 2024, 8:33 p.m.

Panel Version: 4.62

I don't know

Comment on list classification: Limited evidence for green rating. Should be reviewed at the next major review of this panel.

Created: 11 Sep 2020, 1:14 p.m. | Last Modified: 11 Sep 2020, 1:14 p.m.

Panel Version: 2.65

Associated with Microphthalmia, syndromic 3/Optic nerve hypoplasia and abnormalities of the central nervous system #206900 (AD) in OMIM which has hearing loss listed as one of the clinical features.

Summary: 2 individuals (1 in Zhang, 1 in Hagstrom) reported with hearing loss but the optic phenotype is far more predominant.

PMID: 30262714 - Zhang et al 2018 - report a Chinese infant with bilateral clinical anophthalmia and sensorineural hearing loss and a de novo 20bp deletion in SOX2 ( c.70_89del (p. Asn24ArgfsX65; rs398123693)) was identified in targeted sequencing of this gene. This variant has been previously reported in 13 patients from 12 unrelated pedigrees but this is the first time hearing loss has been reported.

PMID: 16932809 - Kelberman et al 2006 - Mouse model - heterozygous mice with a targeted disruption of Sox2 did not manifest eye defects, but showed abnormal anterior pituitary development with reduced levels of growth hormone, luteinizing hormone, and thyroid-stimulating hormone. Also report 8 individuals (from a cohort of 235 patients) screened for variants in SOX2. Hearing loss not reported in these patients.

16145681 - Hagstrom et al 2005 - surveyed 93 patients with severe eye malformations for mutations in SOX2. They report one female patient with bilateral clinical anophthalmia, absence of all optic pathways, as well as modest bilateral sensorineural hearing loss, and global developmental delay. She was heterozygous for a de novo c.463C > T alteration, which predicts p.Q155X.

Created: 11 Sep 2020, 1:10 p.m. | Last Modified: 11 Sep 2020, 1:10 p.m.

Panel Version: 2.63

I don't know

3 individuals with deafness as part of the phenotype but the majority do not have hearing loss. SOX2 mouse models but can't find evidence that hearing was studied/impaired.

Created: 29 Jan 2020, 7:02 a.m. | Last Modified: 29 Jan 2020, 7:02 a.m.

Panel Version: 2.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Microphthalmia, syndromic 3, MIM# 206900

Publications

• 30262714
• 16932809
• 16145681

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
#206900:Optic nerve hypoplasia and abnormalities of the central nervous system[Short stature; Growth failure, postnatal; Microcephaly; Frontal bossing; Hearing loss, sensorineural; MicrophthalmiaAnophthalmia, clinicalOptic nerve hypoplasiaColoboma; Multiple supernumerary teeth (rare); Ventricular septal defect; Patent ductus arteriosus; Absent ribsExtra ribsFused ribs; Esophageal atresia; HypospadiasMicropenis; Cryptorchidism; HemivertebraeUnderdeveloped vertebraeFused vertebraeButterfly vertebrae; Reduction of white matter, generalizedHypothalamic hamartomaMesial temporal brain malformationsAgenesis of corpus callosumHypoplasia of corpus callosumAnterior pituitary hypoplasiaLearning difficultiesPsychomotor delayHypotoniaSpastic diplegiaSpastic quadriplegia; Anterior pituitary hypoplasiaHypogonadotropic hypogonadism; Caused by mutation in the SRY (sex determining region Y)-box 2 gene (SOX2,)]

Publications

• PMID:10564870
• 11135495
• 12002146
• 12036291
• 12461687
• 12612584
• 14517545
• 15240551
• 15346919
• 15389708
• 15812812
• 15846349
• 16145681
• 16283891
• 16470798
• 16543359
• 16651659
• 16712695
• 16892407
• 16904174
• 16932809
• 17015430
• 17219395
• 17515932
• 17522155
• 17554336
• 17554338
• 18029452
• 18157115
• 18285410
• 18385377
• 18806776
• 18818365
• 18831064
• 18845712
• 19254784
• 19403656
• 19801978
• 19898493
• 19921648
• 20803647
• 21326281
• 21331042
• 21532573
• 21919124
• 24048479
• 24909994
• 7849401
• 8741917

Comment on list classification: Good evidence from expert reviewer and OMIM

Created: 31 Jan 2016, 8:04 p.m.