A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient
Abstract Background Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL; OMIM# 615381) is a rare autosomal dominant disorder, with only a few reported cases worldwide. Herein, we describe the clinical features and underlying molecular etiology of MDPL syndrome in an...
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BMC
2022-10-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-022-01374-x |
| _version_ | 1811198020911366144 |
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| author | Bin Zuo Hongen Xu Zhaoyu Pan Lu Mao Haifeng Feng Beiping Zeng Wenxue Tang Wei Lu |
| author_facet | Bin Zuo Hongen Xu Zhaoyu Pan Lu Mao Haifeng Feng Beiping Zeng Wenxue Tang Wei Lu |
| author_sort | Bin Zuo |
| collection | DOAJ |
| description | Abstract Background Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL; OMIM# 615381) is a rare autosomal dominant disorder, with only a few reported cases worldwide. Herein, we describe the clinical features and underlying molecular etiology of MDPL syndrome in an 8-year-old Chinese patient. Methods We performed otological, endocrine, ultrasound, and radiological examinations, as well as genetic testing. Additionally, the literature concerning MDPL was reviewed to do a retrospective analysis of the pathogenesis, genotype–phenotype correlation, and clinical management. Results The proband was diagnosed with MDPL, presenting with mandibular hypoplasia, a characteristic facial appearance, lipodystrophy, and sensorineural hearing loss (SNHL). Whole-exome sequencing and bioinformatics analysis revealed a de novo missense variant in the POLD1 gene, NM_002691.4:c.3185A>G (NP_002682.2:p.(Gln1062Arg)). The retrospective analysis showed wide variation in the MDPL phenotype, but the most frequent features included mandibular hypoplasia, characteristic facial appearance, lipodystrophy, and SNHL. Conclusions This study supplements the mutational spectrum of POLD1. The genetic analysis contributes to the diagnosis of syndromic deafness, and it has a vital role in clinical management and future genetic consultation. |
| first_indexed | 2024-04-12T01:24:01Z |
| format | Article |
| id | doaj.art-456d8b566bfc4180b6aedb7051888073 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-04-12T01:24:01Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-456d8b566bfc4180b6aedb70518880732022-12-22T03:53:42ZengBMCBMC Medical Genomics1755-87942022-10-011511810.1186/s12920-022-01374-xA likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patientBin Zuo0Hongen Xu1Zhaoyu Pan2Lu Mao3Haifeng Feng4Beiping Zeng5Wenxue Tang6Wei Lu7Department of Otorhinolaryngology, The First Affiliated Hospital of Zhengzhou UniversityPrecision Medicine Center, Academy of Medical Science, Zhengzhou UniversityDepartment of Otorhinolaryngology, The First Affiliated Hospital of Zhengzhou UniversityPrecision Medicine Center, Academy of Medical Science, Zhengzhou UniversityDepartment of Otorhinolaryngology, The First Affiliated Hospital of Zhengzhou UniversityPrecision Medicine Center, Academy of Medical Science, Zhengzhou UniversityThe Research and Application Center of Precision Medicine, The Second Affiliated Hospital of Zhengzhou UniversityDepartment of Otorhinolaryngology, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL; OMIM# 615381) is a rare autosomal dominant disorder, with only a few reported cases worldwide. Herein, we describe the clinical features and underlying molecular etiology of MDPL syndrome in an 8-year-old Chinese patient. Methods We performed otological, endocrine, ultrasound, and radiological examinations, as well as genetic testing. Additionally, the literature concerning MDPL was reviewed to do a retrospective analysis of the pathogenesis, genotype–phenotype correlation, and clinical management. Results The proband was diagnosed with MDPL, presenting with mandibular hypoplasia, a characteristic facial appearance, lipodystrophy, and sensorineural hearing loss (SNHL). Whole-exome sequencing and bioinformatics analysis revealed a de novo missense variant in the POLD1 gene, NM_002691.4:c.3185A>G (NP_002682.2:p.(Gln1062Arg)). The retrospective analysis showed wide variation in the MDPL phenotype, but the most frequent features included mandibular hypoplasia, characteristic facial appearance, lipodystrophy, and SNHL. Conclusions This study supplements the mutational spectrum of POLD1. The genetic analysis contributes to the diagnosis of syndromic deafness, and it has a vital role in clinical management and future genetic consultation.https://doi.org/10.1186/s12920-022-01374-xMandibular hypoplasia, progeroid features, and lipodystrophy syndromeMDPLSensorineural hearing lossPOLD1 |
| spellingShingle | Bin Zuo Hongen Xu Zhaoyu Pan Lu Mao Haifeng Feng Beiping Zeng Wenxue Tang Wei Lu A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient BMC Medical Genomics Mandibular hypoplasia, progeroid features, and lipodystrophy syndrome MDPL Sensorineural hearing loss POLD1 |
| title | A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient |
| title_full | A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient |
| title_fullStr | A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient |
| title_full_unstemmed | A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient |
| title_short | A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient |
| title_sort | likely pathogenic pold1 variant associated with mandibular hypoplasia deafness progeroid features and lipodystrophy syndrome in a chinese patient |
| topic | Mandibular hypoplasia, progeroid features, and lipodystrophy syndrome MDPL Sensorineural hearing loss POLD1 |
| url | https://doi.org/10.1186/s12920-022-01374-x |
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