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Case Reports
. 2022 Oct 21;15(1):220.
doi: 10.1186/s12920-022-01374-x.

A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient

Bin Zuo #  1 , Hongen Xu #  2   3 , Zhaoyu Pan  1 , Lu Mao  2 , Haifeng Feng  1 , Beiping Zeng  2 , Wenxue Tang  4   5 , Wei Lu  6
Affiliations
Case Reports

A likely pathogenic POLD1 variant associated with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome in a Chinese patient

Bin Zuo et al. BMC Med Genomics. .

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.

Keywords: MDPL; Mandibular hypoplasia, progeroid features, and lipodystrophy syndrome; POLD1; Sensorineural hearing loss.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Pedigree and Sanger sequencing of the MDPL family. a Pedigree of the MDPL family. b Sanger sequencing
Fig. 2
Fig. 2
Facial phenotype, audiogram, and X-ray of the proband. a Bilateral severe sensorineural hearing loss revealed by pure-tone audiometry showed. The use of hearing aids led to a successful outcome. b When she was 6 years old, the bone age was only 3 years. X-ray showing crowded teeth and mandibular hypoplasia
See this image and copyright information in PMC

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References

    1. Shastry S, Simha V, Godbole K, Sbraccia P, Melancon S, Yajnik CS, Novelli G, Kroiss M, Garg A. A novel syndrome of mandibular hypoplasia, deafness, and progeroid features associated with lipodystrophy, undescended testes, and male hypogonadism. J Clin Endocrinol Metab. 2010;95(10):E192–197. doi: 10.1210/jc.2010-0419. - DOI - PMC - PubMed
    1. Weedon MN, Ellard S, Prindle MJ, Caswell R, Lango Allen H, Oram R, Godbole K, Yajnik CS, Sbraccia P, Novelli G, et al. An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy. Nat Genet. 2013;45(8):947–950. doi: 10.1038/ng.2670. - DOI - PMC - PubMed
    1. Lessel D, Hisama FM, Szakszon K, Saha B, Sanjuanelo AB, Salbert BA, Steele PD, Baldwin J, Brown WT, Piussan C, et al. POLD1 germline mutations in patients initially diagnosed with werner syndrome. Hum Mutat. 2015;36(11):1070–1079. doi: 10.1002/humu.22833. - DOI - PMC - PubMed
    1. Pan Z, Xu H, Tian Y, Liu D, Liu H, Li R, Dou Q, Zuo B, Zhai R, Tang W, et al. Perrault syndrome: clinical report and retrospective analysis. Mol Genet Genomic Med. 2020;8(10):e1445. doi: 10.1002/mgg3.1445. - DOI - PMC - PubMed
    1. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–424. doi: 10.1038/gim.2015.30. - DOI - PMC - PubMed

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