Kachmar Jessica, El-Haffaf Zaki, Bollée Guillaume
Division of Nephrology, Department of Medicine, Centre Hospitalier de l'Université de Montréal, QC, Canada.
Department of Genetics, Centre Hospitalier de l'Université de Montréal, QC, Canada.
Can J Kidney Health Dis. 2023 Oct 18;10:20543581231203054. doi: 10.1177/20543581231203054. eCollection 2023.
Due to next-generation sequencing, variants in new genes such as are recently being identified as causing atypical autosomal dominant polycystic kidney disease (ADPKD). It is important to describe phenotypes associated with these variants in order to increase awareness among clinicians, especially since genetic variability affects ADPKD severity.
We describe a 55-year-old female patient of Haitian origin who presented with slowly deteriorating kidney function, microscopic hematuria, proteinuria, enlarged kidneys with innumerable small cysts, and a family history of chronic kidney disease and cysts. The phenotype was atypical for ADPKD caused by or variants, since cysts were of small size, kidneys were only moderately enlarged, and the patient had no extra-renal involvement suggestive of typical ADPKD such as liver cysts, pancreatic cysts, cranial aneurysms, or cardiac abnormalities.
A panel of genes was analyzed by next-generation massive sequencing techniques, including , and . Genetic testing revealed a heterozygous variant in the gene (c.123 dup), which is predicted to result in premature protein termination (p. Lys42*) and was classified by the laboratory as likely pathogenic.
She was treated with candesartan 16 mg once daily to address her proteinuria.
At the time of the most recent follow-up, her proteinuria has increased, and her kidney function continues to slowly deteriorate.
variants are a rare cause of atypical ADPKD. It is important to recognize the clinical features that help distinguish from and variants. Atypical ADPKD due to variants is usually characterized by small cysts, normal kidney size, proteinuria, progressive chronic kidney disease, and phenotypic overlap with autosomal dominant tubulointerstitial kidney disease (ADTKD). It may, however, present itself with enlarged kidneys as was seen in our patient. Genetic testing should be offered whenever a patient presents atypical features of ADPKD, which also requires increased awareness among clinicians regarding the various phenotypes of atypical ADPKD.
由于新一代测序技术的应用，诸如 等新基因中的变异最近被鉴定为导致非典型常染色体显性多囊肾病（ADPKD）的原因。描述与这些变异相关的表型很重要，以便提高临床医生的认识，特别是因为基因变异性会影响ADPKD的严重程度。
我们描述了一位55岁的海地裔女性患者，她出现肾功能逐渐恶化、镜下血尿、蛋白尿、肾脏增大伴无数小囊肿，以及慢性肾病和囊肿家族史。该表型对于由 或 变异引起的ADPKD来说是非典型的，因为囊肿较小，肾脏仅中度增大，且患者没有提示典型ADPKD的肾外表现，如肝囊肿、胰腺囊肿、颅内动脉瘤或心脏异常。
通过新一代大规模测序技术分析了一组基因，包括 、 和 。基因检测发现 基因存在杂合变异（c.123 dup），预计会导致蛋白质过早终止（p.Lys42*），实验室将其分类为可能致病。
她每天服用一次16毫克坎地沙坦来治疗蛋白尿。
在最近一次随访时，她的蛋白尿增加，肾功能继续缓慢恶化。
变异是导致非典型ADPKD的罕见原因。识别有助于区分 与 及 变异的临床特征很重要。由 变异引起的非典型ADPKD通常表现为小囊肿、肾脏大小正常、蛋白尿、进行性慢性肾病，以及与常染色体显性肾小管间质性肾病（ADTKD）的表型重叠。然而，它也可能像我们的患者那样表现为肾脏增大。每当患者出现ADPKD的非典型特征时，都应进行基因检测，这也需要临床医生提高对非典型ADPKD各种表型的认识。
