Tooth agenesis related to a novel KDF1 variant: A case report and literature review.

IF 2.9 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Oral diseases Pub Date : 2024-11-01 Epub Date: 2024-03-19 DOI:10.1111/odi.14930

Narin Intarak, Chawan Manaspon, Thanakorn Theerapanon, Sasiprapa Prommanee, Lakshman Samaranayake, Vorasuk Shotelersuk, Thantrira Porntaveetus

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引用次数: 0

Abstract

Objectives: To investigate the role of Keratinocyte Differentiation Factor 1 (KDF1) in ectodermal dysplasia (ED) and nonsyndromic tooth agenesis (NSTA) and perform a literature review.

Methods: Genome sequencing was used to identify genetic variants in a Thai, NSTA proband and validated through Sanger sequencing. Pathogenicity was assessed using ACMG guidelines, MetaRNN and AlphaMissense. A comprehensive review of KDF1/NSTA cases informed genotype-phenotype analysis of the proband.

Results: The proband revealed multiple missing teeth, caries and extensive periodontal disease. Deep phenotyping showed no signs of ED beyond tooth agenesis. The identified novel KDF1 variant, p.Ile243Leu, was classified as 'likely pathogenic' by ACMG and predicted as 'detrimental' by MetaRNN and AlphaMissense analyses. A total of 14 reviewed KDF1 cases revealed ED-associated variants (3 variants in 8 patients) clustering in the region of amino acids 251-275, within the DUF4656 domain, while NSTA-causing variants (4 variants in 6 patients) were typically found in amino- or carboxy-termini to this region. KDF1/NSTA cases exhibited an average of 15 missing teeth, with a higher prevalence in the mandible.

Conclusion: This study identifies a novel KDF1 variant-related NSTA in Thai people. The genotype-phenotype correlates suggest a distinctive pattern and tooth agenesis of KDF1-related NSTA.

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与新型 KDF1 变异有关的牙齿缺失：病例报告和文献综述。

研究目的研究角质细胞分化因子 1（KDF1）在外胚层发育不良（ED）和非综合征性牙齿缺失（NSTA）中的作用，并进行文献综述：方法：利用基因组测序确定一名泰国 NSTA 感染者的基因变异，并通过 Sanger 测序进行验证。使用 ACMG 指南、MetaRNN 和 AlphaMissense 评估致病性。对 KDF1/NSTA 病例的全面回顾为该病例的基因型-表型分析提供了依据：结果：该患者有多颗牙齿缺失、龋齿和广泛的牙周病。深度表型分析表明，除牙齿缺失外，没有其他 ED 迹象。经鉴定的新型 KDF1 变异 p.Ile243Leu 被 ACMG 定义为 "可能致病"，并被 MetaRNN 和 AlphaMissense 分析预测为 "有害"。在总共 14 例 KDF1 病例中，发现了 ED 相关变异（8 例患者中有 3 个变异），这些变异聚集在 DUF4656 结构域内的 251-275 氨基酸区域，而 NSTA 致病变异（6 例患者中有 4 个变异）通常出现在该区域的氨基端或羧基端。KDF1/NSTA病例平均有15颗牙齿缺失，下颌骨缺失率较高：本研究在泰国人中发现了一种新型 KDF1 变体相关 NSTA。基因型与表型的相关性表明，KDF1相关NSTA具有独特的模式和牙齿缺失。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oral diseases 医学-牙科与口腔外科

CiteScore

7.60

自引率

5.30%

发文量

325

审稿时长

4-8 weeks

期刊介绍： Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.