Monogenic hearing loss

Gene: MITF

Green List (high evidence)

PMID: 30117279 Rauschendorf et al., 2019
Homozygous intronic MITF mutation causes severe Waardenburg syndrome type 2A. Report of a 6 month old Argentinian boy, parents were siblings. Proband homozygous for intronic MITF c.33+5G>C variant, which co-segregated with less severe features in heterozygous family members. The proband presented with congenital bilateral deafness, hair and skin depigmentation, and iris pigmentation abnormalities. Variant was previously reported in heterozygous state in a patient with Waardenburg syndrome in PMID: 21373256 Haddad et al., 2011.

PMID: 32728090 Thongpradit et al., 2020
Identified a homozygous c.1022G>A: p.Arg341His variant of MITF, which co-segregated with non-syndromic hearing loss in five affected children of a consanguineous hearing couple.

Created: 16 Feb 2026, 1:20 p.m. | Last Modified: 16 Feb 2026, 1:31 p.m.

Panel Version: 5.51

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
hearing loss, autosomal recessive, MONDO:0019588; Waardenburg syndrome, type 2A, OMIM:193510; COMMAD syndrome, OMIM:617306

Publications

• 30117279
• 32728090

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

There is evidence to suggest there is reduced penetrance for this gene-disease association (PMID: 26100139). Due to feedback from Rowenna Roberts at GOSH, this gene has therefore been denoted as having incomplete pentrance.

Created: 17 Mar 2020, 11:19 a.m. | Last Modified: 17 Mar 2020, 11:19 a.m.

Panel Version: 2.8

Comment on mode of inheritance: Confirmed with Maria Bitner-Glindzicz (UCL) that the mode of inheritance should be changed from monoallelic to both monoallelic and biallelic, to cover COMMAD syndrome, after suggestion from another reviewer.

Created: 14 Aug 2018, 7:51 a.m.

Comment on publications: PMID: 27889061 - report of two patients with biallelic variants in this gene with COLOBOMA, OSTEOPETROSIS, MICROPHTHALMIA, MACROCEPHALY, ALBINISM, AND DEAFNESS (COMMAD syndrome) from two families. This is a probable DD gene for COMMAD syndrome.

Created: 1 Jun 2018, 2:59 p.m.

Comment on list classification: Confirmed DD gene.

Created: 17 Feb 2016, 5:01 p.m.

Green List (high evidence)

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

Phenotypes
#103470:Waardenburg syndrome/ocular albinism, digenic[Reduced visual acuity; Photophobia; Nystagmus; Translucent irides; Strabismus; Hypermetropia; Albinotic fundus; Foveal hypoplasia; Optic nerve dysplasia; Hypomelanosis; Lentigines; Deafness; Vestibular hypofunction; Macromelanosomes]; #103500:Tietz albinism-deafness syndrome[Hearing loss, sensorineural, bilateral profound congenital; White eyelashesWhite eyebrowsBlue eyesNo heterochromia iridisHypopigmented fundi; Fair skin; White eyelashesWhite eyebrowsWhite-blonde hair]; #193510:Waardenburg syndrome, type 2A[Deafness, congenital sensorineural; Dystopia canthorum absentHeterochromia iridisHypoplastic iris stomaSynophrys; Wide nasal bridgeHypoplastic alae nasi; Congenital partial albinism (leukoderma) on face, trunk, or limbs; White forelockWhite eyelashes and eyebrowsPremature graying of hair]; #614456:{Melanoma, cutaneous malignant, susceptibility to, 8}

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

Created: 31 Jan 2016, 7:51 p.m.

Green List (high evidence)

Good evidence for causing Waardenburg syndrome and the diagnosis could be missed so put on green list.

Created: 19 Oct 2015, 5:59 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted