A novel <scp><i>MPZL2</i></scp> c.<scp>68delC</scp> variant is associated with progressive hearing loss in Chinese population and literature review

Wang, Zhili; Jiang, Mengda; Wu, Hao; Li, Yun; Chen, Ying

doi:10.1002/lio2.829

Cited by 5 publications

(7 citation statements)

References 23 publications

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“…By comparing the hearing level at the rst consultation and follow-up, we observed that 35.71% (10/28) patients had reduced hearing; however, the progression of HL could not be determined in 2 patients (patients no.34 and 35) in this study. The rate of HL was 2.10 and 13.33 dBHL per year in patient nos.30 and 37, respectively, which is higher than that reported in the literature (0.59 dBHL/year) [15]. A total of 64.29% (18/28) of patients did not report reduced hearing.…”

Section: Discussioncontrasting

confidence: 60%

“…Moreover, the Mpzl2 mutant mice showed early-onset progressive HL and a signi cantly increased ABR threshold [5], which was similar to the ndings in human. However, the rate of HL development in the Mpzl2 mutant mice was much faster than that in humans, and the HL in Mpzl2 mutant mice rapidly developed to moderate and severe at 8 and 12 weeks, respectively (ABR threshold higher than 70 dB SPL) [5,15]. To better demonstrated the extent of HL caused by MPZL2 variants, we combined our results with those from previous studies (a total of 39 cases in Table 1) to comprehensively analyze the genotype and phenotype correlation of the MPZL2 variant.…”

Section: Discussionmentioning

confidence: 99%

“…The recent studies on DFNB111 have mainly focused on the Dutch, Moroccan, and some Middle Eastern countries [5,11,12]. In East Asia countries such as Korea [13,14] and China [15], only a few families were identi ed with these defects and to date, no systematic phenotype-genotype correlation analysis for MPZL2 has been performed.…”

Section: Introductionmentioning

confidence: 99%

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MPZL2—A common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population

Zhang,

Yang,

Wang

et al. 2023

Preprint

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Background: Mutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss. Methods: In this study, we analyzed the phenotype and genotype of 8 pedigrees consisting of 10 deaf patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing. Results: Apart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 13.11% (8/61) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, and MPZL2 variants. Three known MPZL2 variants (c.220C>T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G>T (p.Met1?)) were identified. A 3D model of wild type and mutants of myelin protein zero-like 2 (MPZL2) was constructed and spatial structure analysis revealed that mutational susceptibility in the signal peptide domain might be explained by the instability of the loop structure. By allele frequency analysis, MPZL2 c.220C>T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia. Conclusions: We concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL, although no specified variant was verified for the progression of HL, and the penetrance and expressivity cannot be determined yet. A novo MPZL2 variant at the start codon was identified which enriched the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2.

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Section: Discussioncontrasting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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MPZL2—A common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population

Zhang,

Yang,

Wang

et al. 2023

Preprint

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“…(Pro23-Leufs*2) and c.463del,p. (Ala155Leufs*10) truncating variants have each been reported in the compound heterozygous state with one of the recurrent variants or in the homozygous state in three individuals (Table 1) (Kim et al, 2020;Wang et al, 2022). Finally, a missense variant of uncertain significance, c.52C>T,p.…”

Section: Introductionmentioning

confidence: 99%

Recurrent missense variant identified in two unrelated families with MPZL2‐related hearing loss, expanding the variant spectrum associated with DFNB111

Lo,

Blair,

Yamamoto

et al. 2024

American J of Med Genetics Pt A

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MPZL2‐related hearing loss is a rare form of autosomal recessive hearing loss characterized by progressive, mild sloping to severe sensorineural hearing loss. Thirty‐five previously reported patients had biallelic truncating variants in MPZL2, with the exception of one patient with a missense variant of uncertain significance and a truncating variant. Here, we describe the clinical characteristics and genotypes of five patients from four families with confirmed MPZL2‐related hearing loss. A rare missense likely pathogenic variant [NM_005797.4(MPZL2):c.280C>T,p.(Arg94Trp)] located in exon 3 was confirmed to be in trans with a recurrent pathogenic truncating variant that segregated with hearing loss in three of the patients from two unrelated families. This is the first recurrent likely pathogenic missense variant identified in MPZL2. Apparently milder or later‐onset hearing loss associated with rare missense variants in MPZL2 indicates that some missense variants in this gene may cause a milder phenotype than that resulting from homozygous or compound heterozygous truncating variants. This study, along with the identification of truncating loss of function and missense MPZL2 variants in several diverse populations, suggests that MPZL2‐related hearing loss may be more common than previously appreciated and demonstrates the need for MPZL2 inclusion in hearing loss testing panels.

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“…The recent studies on DFNB111 have mainly focused on the Dutch, Moroccan, and some Middle Eastern countries [ 8 , 14 , 15 ]. In East Asia countries such as Korea [ 4 , 16 ] and China [ 17 ], only a few families were identified with these defects and to date, no systematic phenotype-genotype correlation analysis for MPZL2 has been performed.…”

Section: Introductionmentioning

confidence: 99%

MPZL2—a common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population

Zhang,

Yang,

Wang

et al. 2024

BMC Med Genomics

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Background Mutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss. Methods In this study, we analyzed the phenotype and genotype of eight pedigrees consisting of 10 hearing loss patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing. Results Apart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 7.02% (8/114) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, MPZL2 and others. Three known MPZL2 variants (c.220C > T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G > T (p.Met1?)) were identified. MPZL2 c.220C > T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia through allele frequency. Conclusions We concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL. No specified variant was verified for the progression of HL, the penetrance and expressivity cannot be determined yet. A novel MPZL2 variant at the start codon was identified, enriching the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2.

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A novel MPZL2 c.68delC variant is associated with progressive hearing loss in Chinese population and literature review

Cited by 5 publications

References 23 publications

MPZL2—A common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population

MPZL2—A common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population

Recurrent missense variant identified in two unrelated families with MPZL2‐related hearing loss, expanding the variant spectrum associated with DFNB111

MPZL2—a common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population

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