Atypical ADPKD Due to a Pathogenic Variant: An Educational Case Report
Rationale: Due to next-generation sequencing, variants in new genes such as DNAJB11 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 clini...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2023-10-01
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| Series: | Canadian Journal of Kidney Health and Disease |
| Online Access: | https://doi.org/10.1177/20543581231203054 |
| _version_ | 1797657145775226880 |
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| author | Jessica Kachmar Zaki El-Haffaf Guillaume Bollée |
| author_facet | Jessica Kachmar Zaki El-Haffaf Guillaume Bollée |
| author_sort | Jessica Kachmar |
| collection | DOAJ |
| description | Rationale: Due to next-generation sequencing, variants in new genes such as DNAJB11 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. Presenting Concerns of the Patient: 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 PKD1 or PKD2 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. Diagnoses: A panel of genes was analyzed by next-generation massive sequencing techniques, including DNAJB11, DZIP1L, GANAB, HNF1B, PKD1, PKD2 , and PKHD1 . Genetic testing revealed a heterozygous variant in the DNAJB11 gene (c.123 dup), which is predicted to result in premature protein termination (p. Lys42*) and was classified by the laboratory as likely pathogenic. Interventions: She was treated with candesartan 16 mg once daily to address her proteinuria. Outcomes: At the time of the most recent follow-up, her proteinuria has increased, and her kidney function continues to slowly deteriorate. Teaching Points: DNAJB11 variants are a rare cause of atypical ADPKD. It is important to recognize the clinical features that help distinguish DNAJB11 from PKD1 and PKD2 variants. Atypical ADPKD due to DNAJB11 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. |
| first_indexed | 2024-03-11T17:40:09Z |
| format | Article |
| id | doaj.art-cccc9dc97c1846dc9b4fad06d422a693 |
| institution | Directory Open Access Journal |
| issn | 2054-3581 |
| language | English |
| last_indexed | 2024-03-11T17:40:09Z |
| publishDate | 2023-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Canadian Journal of Kidney Health and Disease |
| spelling | doaj.art-cccc9dc97c1846dc9b4fad06d422a6932023-10-18T13:03:43ZengSAGE PublishingCanadian Journal of Kidney Health and Disease2054-35812023-10-011010.1177/20543581231203054Atypical ADPKD Due to a Pathogenic Variant: An Educational Case ReportJessica Kachmar0Zaki El-Haffaf1Guillaume Bollée2Division of Nephrology, Department of Medicine, Centre Hospitalier de l’Université de Montréal, QC, CanadaDepartment of Genetics, Centre Hospitalier de l’Université de Montréal, QC, CanadaDivision of Nephrology, Department of Medicine, Centre Hospitalier de l’Université de Montréal, QC, CanadaRationale: Due to next-generation sequencing, variants in new genes such as DNAJB11 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. Presenting Concerns of the Patient: 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 PKD1 or PKD2 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. Diagnoses: A panel of genes was analyzed by next-generation massive sequencing techniques, including DNAJB11, DZIP1L, GANAB, HNF1B, PKD1, PKD2 , and PKHD1 . Genetic testing revealed a heterozygous variant in the DNAJB11 gene (c.123 dup), which is predicted to result in premature protein termination (p. Lys42*) and was classified by the laboratory as likely pathogenic. Interventions: She was treated with candesartan 16 mg once daily to address her proteinuria. Outcomes: At the time of the most recent follow-up, her proteinuria has increased, and her kidney function continues to slowly deteriorate. Teaching Points: DNAJB11 variants are a rare cause of atypical ADPKD. It is important to recognize the clinical features that help distinguish DNAJB11 from PKD1 and PKD2 variants. Atypical ADPKD due to DNAJB11 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.https://doi.org/10.1177/20543581231203054 |
| spellingShingle | Jessica Kachmar Zaki El-Haffaf Guillaume Bollée Atypical ADPKD Due to a Pathogenic Variant: An Educational Case Report Canadian Journal of Kidney Health and Disease |
| title | Atypical ADPKD Due to a Pathogenic Variant: An Educational Case Report |
| title_full | Atypical ADPKD Due to a Pathogenic Variant: An Educational Case Report |
| title_fullStr | Atypical ADPKD Due to a Pathogenic Variant: An Educational Case Report |
| title_full_unstemmed | Atypical ADPKD Due to a Pathogenic Variant: An Educational Case Report |
| title_short | Atypical ADPKD Due to a Pathogenic Variant: An Educational Case Report |
| title_sort | atypical adpkd due to a pathogenic variant an educational case report |
| url | https://doi.org/10.1177/20543581231203054 |
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