Table 1.
Clinical Presentation and Pathogenic Variants in the 23 Affected Individuals from Seven DNAJB11-Affected Families
| Family | Pathogenic Variant | Subject | Sex | eGFRa(age) or ESRD (age) | Context of Diagnosis (age) | HBP (age)b |
Morphology of the Kidneys |
Liver Cysts (number) | Other Significant Conditions (age) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Type | Age | Description of the Cysts | Kidney Length, (TKVml)c | Figure | |||||||||
| 1 d | c.161C>G (p.Pro54Arg) | I.1 | F | 28 (79) | renal insufficiency (78) | yes (60) | MRI | 80 | multiple bilateral small cysts (mostly < 1 cm, largest 2 cm) | R:9.2, L:10 (323) | 1B | yes (3) | epilepsy (10) |
| II.1 | F | 96 (45) | incidental (43) | no (45) | MRI | 44 | multiple bilateral small cysts (largest 1.3 cm) | R:9.5, L:10 (335) | 1C | yes (10) | metanephric adenoma, partial nephrectomy (43) | ||
| III.1 | F | 93 (19) | familial study (19) | no (19) | MRI | 19 | no renal cysts | R:9.7, L:10.0 (277) | NA | no | none | ||
| 2 d | c.166_167insTT (p.Arg56fs) | II.1 | M | 54 (66) | familial study (na) | yes (56) | MRI | 53 | multiple bilateral small cysts (largest 0.8 cm) | NA | NA | no | parathyroid adenoma, hypertrophic cardiomyopathy |
| II.2e | F | 84 (76) | familial study (61) | yes (∼50) | CT | 70 | small cortical cysts in the left kidney | R: 9.5, L: 9.6 | S1A | yes (> 50) | Parkinson disease (60) | ||
| III.2 | F | 101 (45) | incidental (31) | no (45) | MRI | 38 | multiple bilateral small cysts | R:11.5, L:12 | 1D | yes (> 50) | breast cancer (36) | ||
| III.3 | F | 77 (56) | familial study (42) | yes (∼50) | US | 42 | three parapelvic cysts on left kidney (largest 1 cm), no cysts detected on left kidney | R:9.7, L:10.6 | NA | yes (> 20) | none | ||
| 3 | c.479delC (p.Ala160fs) | II.1e | F | ESRD (75) | renal insufficiency (∼65) | NA | NA | NA | NA | NA | NA | NA | none |
| II.3 | F | ESRD (89) | NA | NA | CTf | 91 | atrophic kidneys with multiple cysts | R:6; L:6 | S1B | No | none | ||
| III.2 | F | 39 (59) | incidental (57) | yes (51) | US | 57 | multiple bilateral small cysts (largest 1.2 cm) | R:12, L:10 | S1C | yes (na) | glioblastoma (59) | ||
| III.4 | M | 85 (66) | familial study (66) | no (66) | CT | 62 | multiple bilateral small cysts (largest 1.1 cm) | R:11, L:11 (483) | S1D | no | kidney stones (52) | ||
| III.5 | F | 82 (57) | familial study (57) | no (57) | MRI | 57 | multiple bilateral small cysts | R:11, L:11 (300) | 1E | no | none | ||
| IV.2 | M | 97 (36) | familial study (35) | no (35) | MRI | 36 | seven bilateral small cysts (largest 0.3 cm) | R:10, L:9 (299) | S1E | yes (9) | none | ||
| 4 | c.230T>C (p.Leu77Pro) | I.1 | F | ESRD (88) | renal insufficiency (78) | yes (79) | CT | 90 | multiple bilateral small cysts | R:9, L:10 | 1F | no | colorectal cancer (79) |
| II.1 | M | 25 (68) | incidental (65) | yes (48) | MRI | 66 | multiple bilateral small cysts | R:11, L:11 (280) | 1G | no | type 2 diabetes (66) | ||
| 5 | c.616C>T (p.Arg206∗) | I.1e | F | ESRD (84) | autopsy (84) | NA | Autopsy | 84 | multiple bilateral small cysts (mostly < 1 cm, largest 1.5 cm) | R:9.5, L:10 | NA | NA | none |
| II.2 | F | ESRD (59) | incidental (56) | yes (57) | CT | 57 | multiple bilateral small cysts (largest 1 cm) | R:7.7, L:11.5 | NA | no | gastrectomy for peptid ulcer disease (54), gout (50) | ||
| III.1 | F | 82 (56) | incidental (36) | no (57) | MRI | 41 | multiple bilateral small cysts (largest 0.8 cm) | R:9, L:10.5 (353) | 1H | yes (> 10) | gout (39) | ||
| III.2 | M | 67 (55) | familial study (55) | yes (55) | MRI | 55 | four bilateral cysts (largest 0.9 cm) | R:10.4, L:10.7 (450) | NA | no | gout (40) | ||
| IV.1 | F | 92 (20) | familial study (20) | no (20) | NA | NA | NA | NA | NA | NA | epilepsy (8) | ||
| 6 | c.616C>T (p.Arg206∗) | II.2 | M | ESRD (74) | incidental (64) | yes (57) | CT | 74 | multiple bilateral small cysts (largest 2.7cm) | R:10, L:12 (371) | 1I | no | type 2 diabetes (50), psoriatic arthritis (60) |
| II.3 | F | ESRD (70) | renal insufficiency (60) | yes (56) | CT | 71 | multiple bilateral small cysts | R:10, L:9.3 (462) | S1F | no | ischemic cardiomyopathy (71), kidney stones (27) | ||
| 7 | c.616C>T (p.Arg206∗) | II.2 | F | 100 (51) | flank pain (51) | no (52) | MRI | 51 | multiple small renal cysts (largest 2 cm), 3 angiomyolipomas (largest 5 cm) | R:13, L:13 (605) | 1J | yes (> 20) | ischemic colitis (53), hearing loss (48) |
Abbreviations: ACKD, acquired cystic kidney disease; CT, computed tomography; HBP, high blood pressure; MRI, magnetic resonance imaging; NA, not available; TKV, total kidney volume; US, ultrasound examination.
a
Expressed as mL/min/1.73 m2 on the basis of the last data available; obtained with the CKD-EPI formula
b
Age at HBP diagnosis or blood-pressure measurement
c
When available, obtained by stereological measurement; R, right kidney; L, left kidney
d
The pathogenic variant in this pedigree was first identified by whole-exome sequencing
e
A sample was unavailable, and so the DNAJB11 variant was not confirmed
f
Imaging performed 3 years after ESRD