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Hearing loss

Gene: SLITRK6

Amber List (moderate evidence)

SLITRK6 (SLIT and NTRK like family member 6)
EnsemblGeneIds (GRCh38): ENSG00000184564
EnsemblGeneIds (GRCh37): ENSG00000184564
OMIM: 609681, Gene2Phenotype
SLITRK6 is in 1 panel

3 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting this gene from red to amber but with a recommendation for a green rating following GMS review.
Created: 4 Nov 2020, 12:33 p.m. | Last Modified: 4 Nov 2020, 12:33 p.m.
Panel Version: 2.101
Associated with Deafness and myopia #221200 (AR) in OMIM.

PMID: 29551497 - Salime et al 2018 - report a consanguineous Moroccan family with 2 children diagnosed for deafness and myopia in infancy. The SLITRK6 was sequenced and a homozygous 1 bp deletion leading to a premature stop codon p.Trp232Cysfs*10 was found. The parents were heterozygous for the variant as were 3 unaffected siblings.

PMID: 23946138 - Morlet et al 2014 - report 9 Old Order Amish individuals who were homozygous for a nonsense mutation of SLITRK6 (c.1240C>T, p.Gln414Ter) and suffered progressive cochlear and auditory nerve dysfunction

PMID: 23543054 - Tekin et al 2013 - report 3 families (1 old-order Amish family, 1 consanguineous Turkish and 1 Greek).
The Amish and Turkish families had members with congenital myopia and prelingual sensorineural hearing loss, while the affected Greek family had hearing loss only. Homozygous nonsense variants were found in SLITRK6 in all 3 families (Amish p.Q414X, Turkish p.S297X, Greek p.R181X). WES was performed on the Turkish family, targeted sequencing in a region of autozygosity in the Amish family, and targeted SLITRK6 sequencing in the Greek family in which affected members had the same haplotype in that region. Mouse Slitrk6 KO show a hearing loss phenotype.

Summary: founder mutation in SLITRK6 in several Amish families, plus 3 other variants reported in families of other ethnicities. Mouse model shows hearing loss phenotype.
Created: 4 Nov 2020, 12:28 p.m. | Last Modified: 4 Nov 2020, 12:29 p.m.
Panel Version: 2.98

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Deafness and myopia, 221200; high myopia-sensorineural deafness syndrome MONDO:0009082

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Multiple Amish families reported segregating a founder mutation; recent report of another non-Amish family with different variant; mouse model supports gene-disease association. Green or Amber?
Created: 29 Jan 2020, 6:18 a.m. | Last Modified: 29 Jan 2020, 6:18 a.m.
Panel Version: 2.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Deafness and myopia, MIM#221200

Publications

Variants in this GENE are reported as part of current diagnostic practice

Jun Shen (Harvard Medical School)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#221200:Deafness and myopia[Hearing loss, prelingual sensorineural, moderate to severeSymmetric deterioration of hearing loss and speech reception with ageSevere to profound hearing impairment by early adulthoodAbsent distortion product otoacoustic emissions (OAEs)Absent ipsilateral middle ear muscle reflexes (in older patients)Increase in amplitude and duration of cochlear microphonic (CM) (in young patients)Absent cochlear microphonic (in older patients)Bilateral dys-synchronized auditory brainstem responsesNo reproducible waves I, III, or V at high intensitiesAbsence of vestibular evoked myogenic potentials (rare); High myopia; Caused by mutation in the SLIT- and NTRK-like family, member-6 gene (SLITRK6,)]

Publications

Details

Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Deafness and myopia, 221200
  • high myopia-sensorineural deafness syndrome MONDO:0009082
Tags
for-review
OMIM
609681
Clinvar variants
Variants in SLITRK6
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

4 Nov 2020, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: SLITRK6.

4 Nov 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: slitrk6 has been classified as Amber List (Moderate Evidence).

4 Nov 2020, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: SLITRK6 were changed from Deafness and myopia, 221200 to Deafness and myopia, 221200; high myopia-sensorineural deafness syndrome MONDO:0009082

4 Nov 2020, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: SLITRK6 were set to

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SLITRK6 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen