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Hearing loss

Gene: MPZL2

Amber List (moderate evidence)

MPZL2 (myelin protein zero like 2)
EnsemblGeneIds (GRCh38): ENSG00000149573
EnsemblGeneIds (GRCh37): ENSG00000149573
OMIM: 604873, Gene2Phenotype
MPZL2 is in 1 panel

2 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting this gene from grey to amber with a recommendation of a green rating following GMS review. 15 cases reported, 3 different variants. Mouse model supports role of gene in hearing loss.
Created: 19 Nov 2020, 12:18 p.m. | Last Modified: 19 Nov 2020, 12:18 p.m.
Panel Version: 2.111
Associated with Deafness, autosomal recessive 111 #618145 (AR) in OMIM.

15 unrelated families reported but 5 are homozygous for variant c.72delA and 8 for c.220C>T:p.Gln74* in MPZL2. 2 others are compound heterzgyous. A total of 3 variants reported. Founder effects in the Turkey/Iran population were found. In the Korean population no founder effect was detected but the population freq of the c.220C>T:p.Gln74* variant is higher in the Korean/Japanese populations than in other populations. A mouse knockout showed early-onset progressive HI.

PMID: 32203226 Kim et al 2020 - screened 110 pediatric patients from 83 families with mild-to-moderate nonsyndromic SNHL (sporadic and recessive cases only) and identified 9 unrelated individuals with MPZL2-related deafness. 8 patients were homozygous for c.220C>T:p.Gln74*. 1 patient was compound het c.220C>T:p.Gln74*, c.463delG:p.Ala155Leufs*10 (NM_005797.3). They did not find a common haplotype associated with p.Gln74*, but the significantly higher minor allele frequency in Koreans (0.009439) and Japanese (0.01974) compared to overall population frequence (0.0003969) (Gnomad r2.1.1) suggests the allele could be a very old founder allele.

PMID: 29982980 - Bademci et al 2018 - report 3 unrelated consanganious families from Turkey and Iran with autosomal recessive nonsyndromic hearing and a loss and a loss-of-function variant (c.72delA) in MPZL2 which segregates with moderate hearing loss in the families. A shared haplotype flanking the variant in the families suggests a single founder.

PMID: 29961571 - Wesdorp et al 2018 - report 3 families with homozygous truncating variants in MPZL2. In 2 families (1 consanguineous Dutch, the original index case, 1 of Turkish origin (identified by phenotype matching) they identified a homozygous variant (c.72del (p.Ile24Metfs∗22). In a further family of Turkish origin, identified through previous WES, they found compound heterozygous variants in MPZL2 c.72del and c.220C>T (p.Gln74∗). Haplotype analysis of the c.72del MPZL2 alleles showed a shared a haplotype of at least 0.5 Mb, suggesting that it is a founder variant rather than a recurrent variant due to a mutational hotspot. Mpzl2-mutant mice showed early-onset progressive HI.
Created: 19 Nov 2020, 12:16 p.m. | Last Modified: 19 Nov 2020, 12:16 p.m.
Panel Version: 2.110

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal recessive 111 OMIM:618145; deafness, autosomal recessive 111 MONDO:0029142

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

16 individuals from 6 unrelated consanguineous families reported with bi-allelic variants in this gene.
Sources: Expert list
Created: 2 Jan 2020, 5:02 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal recessive 111, MIM#618145

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Deafness, autosomal recessive 111 OMIM:618145
  • deafness, autosomal recessive 111 MONDO:0029142
Tags
for-review
OMIM
604873
Clinvar variants
Variants in MPZL2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

19 Nov 2020, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: MPZL2.

19 Nov 2020, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: MPZL2 were changed from Deafness, autosomal recessive 111, MIM#618145 to Deafness, autosomal recessive 111 OMIM:618145; deafness, autosomal recessive 111 MONDO:0029142

19 Nov 2020, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MPZL2 were set to 29982980; 29961571

19 Nov 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: mpzl2 has been classified as Amber List (Moderate Evidence).

2 Jan 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: MPZL2 was added gene: MPZL2 was added to Hearing loss. Sources: Expert list Mode of inheritance for gene: MPZL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MPZL2 were set to 29982980; 29961571 Phenotypes for gene: MPZL2 were set to Deafness, autosomal recessive 111, MIM#618145 Review for gene: MPZL2 was set to GREEN