Deafness_IsolatedAndComplex

Gene: CD164

Green List (high evidence)

p.(Arg192Ter), a truncating variant that results in loss of 6 amino acids, was detected in two families (one Polish and one Korean) with hearing loss. Four affected (heterozygous) and two unaffected (neg) were tested, however 14 members had been diagnosed with HL in a large multi generational family (gene panel 237 genes). The second family (WES) had two affected heterozygous and no unaffected were tested. This same variant had previously been reported in a Danish family (12 affected heterozygous and 13 unaffected negative, but one younger member unaffected are heterozygous) with hearing loss (PMID: 26197441), for which functional studies in HEK cells demonstrated that the truncated protein was almost completely retained on the plasma cell membrane in contrast to the wild-type protein, which targeted primarily to the endo-lysosomal compartments. The YHTL motif, deleted by the c.574C>T nonsense mutation, is a canonical sorting motif
known to be recognized by specific adaptor proteins in the cytosol, leading to subcellular trafficking of the transmembrane protein to endosomes and lysosomes.

Created: 5 May 2022, 1:37 a.m. | Last Modified: 5 May 2022, 1:37 a.m.

Panel Version: 1.124

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
autosomal dominant nonsyndromic hearing loss MONDO:0019587 CD164-related

Publications

• 35254497
• 26197441

Red List (low evidence)

Single family reported; rated as LIMITED evidence by ClinGen.
Sources: Expert list

Created: 30 Dec 2019, 11:54 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Deafness, autosomal dominant 66, MIM# 616969

Publications

• 26197441