Monogenic hearing loss
Gene: HTRA2Comment on list classification: Demoting from Amber to Red following review by Anna De Burca which notes that hearing loss is only reported in one family, and other phenotypes are more neurological.Created: 28 Feb 2019, 11:49 a.m.
Although as noted by Sarah Leigh, biallelic variants in this gene have been associated with profound sensorineural hearing loss in a single consanguineous family (PMID:27208207), all reported cases have been associated with a severe early-onset neurodegenerative condition. Given the role of HTRA2 in the mitochondrion, it seems plausible that the reported hearing loss is a feature of the phenotype, however it is also possible that there was an independent cause for the hearing loss in this family. Since this panel is targeted primarily at non-syndromic hearing loss, and all of the reported cases to date have had a clearly recognisable, early-onset neurological condition in addition to hearing loss, it seems most appropriate for this gene to be red. It would be appropriate for inclusion in the panel in future if further cases are reported with isolated hearing loss.Created: 12 Feb 2019, 2:31 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Infantile neurodegeneration and 3-methylglutaconic aciduria
Publications
Associated with phenotype in OMIM and as a possible G2P. At least 4 homozygous variants reported in 4 unrelated ethnically diverse families. Segregation with the condition demonstrated for two of the variants (PMID 27208207) and functional studies provided for the remaining two variants (PMID 27696117). However, hearing loss is only reported in one consanguinous familyCreated: 5 Sep 2017, 8:47 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
3-methylglutaconic aciduria, type VIII 617248
Publications
Gene: htra2 has been classified as Red List (Low Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
HTRA2 was added to Congenital hearing impairment (profound/severe)panel. Sources: Literature
HTRA2 was created by sleigh