A rare multisystemic disorder with chronic kidney disease: Karyomegalic interstitial nephritis due to homozygous FAN1 c.2260C>T variant.

IF 2.4 4区医学 Q2 UROLOGY & NEPHROLOGY

Nephrology Pub Date : 2024-09-18 DOI:10.1111/nep.14394

Merve Guzel Dirim,Ahmet Burak Dirim,Berker Kaya,Naci Senkal,Tugba Kalayci,Ayca Aslanger,Neslihan Berker,Murat Kose,Isin Kilicaslan,Halil Yazici

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Abstract

Karyomegalic interstitial nephritis (KIN) is a rare entity associated with biallelic FAN1 (FANCD2/FANCI-Associated Nuclease 1) gene variants. In FAN1-related KIN, abnormal liver function tests and respiratory involvement are common, in addition to chronic kidney disease. Karyomegalic changes have also been reported in many other organs in patients with FAN1-related KIN in various studies. We report the case of a 35-year-old male with chronic kidney disease of unknown aetiology, concurrent recurrent upper and lower respiratory tract infections, and elevated liver function test results with unidentified aetiology. The patient's family history was remarkable for consanguineous parent marriage and history of kidney transplantation in his aunt. A kidney biopsy was performed, which was consistent with KIN. Clinical exome sequencing revealed a homozygous nonsense variant NM_014967.5 (FAN1): c. 2260C > T (p.Arg754Ter). According to the American College of Medical Genetics (ACMG) criteria, this variant is pathogenic and, to the best of our knowledge, has not been previously reported, homozygously. Therefore, the histopathological and clinical diagnoses of KIN were confirmed by genetic studies in our patient. This case report expands the genetic spectrum of FAN1-related KIN, and briefly reviews the current literature data.

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一种伴有慢性肾病的罕见多系统疾病：由同型 FAN1 c.2260C>T 变异引起的巨细胞性间质性肾炎。

巨细胞性间质性肾炎（KIN）是一种罕见的疾病，与双偶性 FAN1（FANCD2/FANCI-Associated Nuclease 1）基因变异有关。在与 FAN1 相关的 KIN 中，除慢性肾病外，肝功能检查异常和呼吸系统受累也很常见。在各种研究中，FAN1 相关 KIN 患者的许多其他器官也出现了巨核细胞病变。我们报告了一例 35 岁男性患者的病例，该患者患有病因不明的慢性肾病、反复发作的上下呼吸道感染以及病因不明的肝功能检测结果升高。该患者的家族史中，父母为近亲结婚，其姑姑曾接受过肾移植手术。患者接受了肾活检，结果与 KIN 一致。临床外显子组测序发现了一个同源无义变异 NM_014967.5 (FAN1)：c. 2260C > T (p.Arg754Ter)。根据美国医学遗传学会（ACMG）的标准，该变异具有致病性，而且据我们所知，以前从未报道过同源变异。因此，我们对患者的基因研究证实了组织病理学和临床诊断为 KIN。本病例报告扩展了 FAN1 相关 KIN 的基因谱，并简要回顾了目前的文献数据。

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

Nephrology 医学-泌尿学与肾脏学

CiteScore

4.50

自引率

4.00%

发文量

128

审稿时长

4-8 weeks

期刊介绍： Nephrology is published eight times per year by the Asian Pacific Society of Nephrology. It has a special emphasis on the needs of Clinical Nephrologists and those in developing countries. The journal publishes reviews and papers of international interest describing original research concerned with clinical and experimental aspects of nephrology.