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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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