Table 2.
Demographics, genetic information, and effect on management for patients with diagnostic genetic results
| Patient Number | Sex | Age(yr) | L1 | L2 | L3 | L4 | L5 | Type of Genetic Testing (1, 2, 3, 4, 5)a | Gene/Locus | Genetic Finding (SNV/Indel/CNV) | Phenotype (Indication for Referral) | Comment |
| RGC-0001 | F | 10 | − | − | + | + | − | 1 | PKD1 | NM_001009944.2: c.7987C>T (p.Q2663*) (het) | Bilateral renal cysts | |
| RGC-0003 | M | 0.8 | − | − | + | + | + | 4 | PKD1 | Partial PKD1 gene deletion (at least exons 27–38) (het) (novel) | Bilateral renal cysts | Subsequently mother was found have cysts in her kidneys |
| RGC-0004 | M | 13 | − | − | + | + | + | 2 | HNF1B | arr[GRCh37]2q36.3 (227999132_228097605)x1 | Chromosomal abnormality | Deletion was found to be maternally inherited |
| RGC-0009 | M | 10 | − | − | + | + | + | 1 | PKD1 | NM_001009944.2: c.7483T>C (p.C2495R) (het) | Bilateral renal cysts and duplicated collecting system | Symptomatic sibling tested positive for KFM |
| RGC-0010 | M | 16 | − | − | − | + | + | 1 | COL4A5 | NM_000495.4: c.152G>T (p.G51V) (hem) | Hematuria and proteinuria | Symptomatic sibling tested positive for KFM |
| RGC-0013 | M | 3 | − | − | − | + | − | 1 | COL4A5 | NM_000495.4: c.3197G>C (p.G1066A) (hem) | Alport syndrome | |
| RGC-0014 | F | 10 | − | − | + | + | − | 2 | 1q21 del | arr[GRCh37]1q21.1q21.2 (146618988–147825855)x1 | Learning disability, VUR, cataracts, microcephaly | Patient also has 16p11.2 0.521 Mb duplication |
| RGC-0018 | M | 1.5 | − | − | + | + | − | 2 | HNF1B | arr[GRCh37] 17q12 (34842059–36214026)x1 | Unilateral multicystic dysplastic kidney, VUR, hypercalcemia, developmental delay, hypotonia | |
| RGC-0019 | F | 16 | − | − | + | − | − | 2, 3 | WDR19 | NM_025132: c.3703G>A (p.E1235K) (het) arr[GRCh37]4p14 (39215680–39219295)x1 | ESKD, dysautonomia, migraines, choledochal and pancreas cyst | |
| RGC-0021 | F | 2.7 | − | − | + | + | + | 2, 4 | PKD1 | NM_001009944.2: c.1259A>G (p.Y420C) (het) | Cystic kidney and Chiari malformation | PKD1 variant is de novo |
| RGC-0026 | F | 4 | − | − | + | − | + | 2, 4 | EYA1 | arr[GRCh37]8q13.2q13.3 (69901440–72586292)x1 | Branchio-oto-renal syndrome | EYA1 variant is de novo |
| RGC-0029 | M | 2.9 | − | − | + | + | − | 1 | PKD1 | NM_001009944.2: c.2659delT (p.W887Gfs*11) (het) | Bilateral renal cysts | |
| RGC-0030 | F | 1.5 | + | − | + | − | + | 1 | NPHS2 | NM_014625: c.790G>C (p.E264Q) (het), and c.779T>A (p.V260E) (het) | Infantile nephrotic syndrome | Phase of the variants were determined (opposite chromosomes), subsequently symptomatic siblings tested positive for these variants |
| RGC-0032 | M | 12 | − | − | + | − | + | 2, 4 | DYRK1A | NM_001396: c. 501delA (p.G168fs) (het) | Intellectual disability and hypospadias | DYRK1A variant is de novo |
| RGC-0034 | F | 2.6 | + | − | + | + | + | 1, 2, 4 | WT1 | NM_024426.4: c.1390G>A (p.D464N) (het) | Atypical HUS | WT1 variant is de novo |
| RGC-0039 | F | 7 | − | − | + | + | + | 2, 4 | COL4A3 | NM_000091: c.1407delA (p.G470fs) (het) and c.40_63del (p.L14_L21del) (het) | Hereditary nephritis | Each variant is inherited from one parent |
| RGC-0041 | M | 15 | − | − | + | − | + | 2 | 22q11 triplication | arr[GRCh37]22q11.1q11.21 (17289827–18640328)x3 | Facial asymmetry, imperforate anus, neurogenic bladder | This triplication is de novo |
| RGC-0043 | M | 11 | − | − | + | − | + | 2, 4 | KAT6B | NM_012330: c.3280delG (p.E1094fs) (het) | Bilateral undescended testes, a mild hypospadias, and Ohdo syndrome | KAT6B variant is de novo |
| RGC-0046 | M | 3 | + | − | + | − | − | 1 | NPHS2 | NM_014625: c.790G>C (p.E264Q) (het), and c.779T>A (p.V260E) (het) | Positive family history of infantile nephrotic syndrome | Avoid immune suppression |
| RGC-0047 | F | 2 | + | − | + | − | − | 1 | NPHS2 | NM_014625: c.790G>C (p.E264Q) (het) and c.779T>A (p.V260E) (het) | Infantile nephrotic syndrome | Avoid immune suppression |
| RGC-0050 | M | 18 | − | − | + | − | + | 2, 4 | TMEM67 | NM_153704: c. 515G>T (p.R172L) (het) and c.1021G>A (p.G341R) (het) (novel) | Joubert syndrome | Each variant is inherited from one parent |
| RGC-0052 | M | 0.8 | − | − | + | + | + | 2, 4 | NSD1 | NM_022455.4: c.3423_3424insCC (p.N1142PfsX11) (het) (novel) | Macrosomia and nephromegaly | NSD1 variant is de novo |
| RGC-0054 | M | 1.9 | + | − | + | − | + | 2, 4 | PLCE1 | NM_016341.3: c.4675_4678delITTAG (p.L1559fs) (hom) (novel) | Nephrotic-range proteinuria | Each variant is inherited from one parent |
| RGC-0055 | M | 10 | − | − | + | + | − | 1 | PKD1 | NM_001009944.2: c.7483T>C (p.C2495R) (het) | Family history of ADPKD, bilateral cystic kidney disease, and duplicated collecting system | |
| RGC-0058 | M | 3 | − | − | − | + | − | 1 | ATP6V0A4 | NM_020632.2: c.1231G>T (p.D411Y) (hom) | Distal renal tubular acidosis | Hearing evaluation was normal |
| RGC-0063 | F | 3 | − | − | − | + | − | 1 | PKD1 | NM_001009944.2: c.7111del (p.V2371Cfs*11) (het) | Bilateral renal cysts | Echocardiogram |
| RGC-0066 | F | 19 | − | + | − | + | + | 2, 4 | USP9X | NM_001039590.2: c.5606_5607dupTC (p.V1870SfsX37) (het) (novel) | Hypertension and Townes–Brocks syndrome | USP9X variant is de novo |
| RGC-0067 | M | 4.9 | − | − | + | + | + | 2, 4 | COL4A5 | NM_000495: c.5034T>A (p.C1678X) (hem) (novel) | Hematuria and thin basement membrane nephropathy | COL4A5 variant is maternally inherited |
| RGC-0068 | M | 14 | − | + | − | + | + | 2, 4 | OCRL | NM_000276.3: c.2531_2539delGAGAACTC TinsAAG (p.R844_L847delinsQV) (hem) (novel) | Cataracts and proteinuria | OCRL variant is maternally inherited, subsequently sibling tested positive for KFM |
| RGC-0070 | F | 13 | − | + | − | + | − | 2, 3 | NPHP4 | NM_015102.3: c.3611C>T (p.P1204L) (hom) | CKD | |
| RGC-0072 | M | 11 | − | − | + | + | − | 2, 3 | PKD1 | NM_001009944: c.9859_9861del (p.L3287del) (het) | Bilateral renal cysts | |
| RGC-0075 | F | 14 | − | − | + | + | − | 2, 3 | DCDC2 | NM_016356: c.383C>G (p.S128X) (hom) | ESKD and liver fibrosis | |
| RGC-0076 | M | 4 | − | − | − | + | + | 1 | COL4A5 | NM_000495.4: c.1948G>A (p.G650S) (hem) | Alport syndrome | Siblings tested negative for KFM |
| RGC-0077 | F | 6 | − | − | + | + | + | 1 | PKD1 | NM_001009944.2: likely pathogenic c.8948+1G>T (het), VUS c.955GG>C (p.Vl3184L) (het) | Bilateral renal cysts | Each variant in PKD1 is inherited from one parent |
| RGC-0078 | F | 1.9 | − | − | + | + | + | 1 | PKD1 | Likely pathogenic c.9829C>T (p.R3277C) (het), VUS c.3494A>G (p. D1165G) (het) | Bilateral renal cysts | Each variant in PKD1 is inherited from one parent |
| RGC-0080 | M | 12 | + | − | + | − | + | 1 | PKHD1 | NM_138694.3: likely pathogenic (c.3761_3762delinsG) (p.A1254Gfs*49) (het), VUS c.4292G>A (p.C1431Y) (het) | Bilateral renal cysts | Pseudodominant ARPKD, each variant is inherited form one parent; both father and paternal aunt are clinically diagnosed with ARPKD |
| RGC-0081 | M | 13 | − | − | − | + | + | 2, 4 | COL4A5 | arr[GRCh37]Xq22.3 (107802035–107802303)x0 (Novel) | Alport syndrome, developmental delay, autism, ADHD | This deletion is maternally inherited |
| RGC-0083 | M | 16 | + | + | − | + | + | 2, 4 | COL4A5 | NM_000495: c.3059dupT (p.G1021fs) (hem) (novel) | FSGS | Both patient and his affected mother’s diagnosis has been changed and avoid immune suppression |
| RGC-0084 | F | 4.9 | + | − | + | − | + | 2, 4 | RMND1 | NM_017909: c.713A>G (p.N238S) (het) and c.533C>T (p.T178M) (het) | CKD, congenital hearing loss, and developmental delay | Each variant is inherited from one parent |
| RGC-0085 | M | 0.5 | − | − | + | − | + | 2, 4 | CASK | NM_003688: c.1721dupA (p.S575fs) (hem) (novel) | Microcephaly, dysmorphic features, right club feet, neurologic dysfunction, hypotonia, pontocerebellar hypoplasia, and right cryptorchidism | Variant in CASK is de novo |
| RGC-0086 | M | 0.2 | − | − | + | + | − | 2 | 1q23.2q25.1 deletion | arr[GRCh37]1q23.2q25.1 (160369890–175796325)x1 | Multiple congenital anomalies including dysplastic ears, dysplastic kidney, bilateral undescended testes, dysmorphic features, and abnormality of the shape of hands | |
| RGC-0087 | M | 9 | − | − | + | + | + | 1 | PKD1 | NM_001009944.2: c.11017–10C>A (IVS37–10C>A) (het) | Bilateral renal cysts | PKD1 variant is inherited from father; subsequently, father and PGF were diagnosed with ADPKD |
| RGC-0088 | F | 6 | − | − | − | + | − | 1 | PKD1 | NM_001009944.2: c.6806C>G (p.S2269*) (het) | Bilateral renal cysts | |
| RGC-0090 | F | 18 | − | − | − | + | − | 1 | COL4A5 | NM_000495.4: c.4602del (p.Y1535Ifs*13) (het) (novel) | Alport syndrome | |
| RGC-0091 | M | 8 | − | − | + | + | − | 2, 3 | PKD1 | NM_001009944.2: c.8043_8046delCTCG (p.S2682Afs*2) (het) (novel) | Bilateral renal cysts | |
| RGC-0092 | F | 2 | − | − | − | + | + | 2, 4 | PKHD1 | NM_138694.3: pathogenic variant c.3761_3762delCCinsG (het), VUS c.10666C>T (p.R3558C) (het) | Bilateral renal cysts | One variant is inherited from one parent and the other one is de novo |
| RGC-0097 | F | 17 | − | − | + | + | + | 4 | COL4A5 | NM_033380.1: c.3631G>A (p.G1211R) (het) | Hereditary nephritis | COL4A5 variant is de novo |
| RGC-0100 | M | 15 | − | − | + | + | − | 1 | HNF1B | NM_000458.2: c.513G>A (p.W171X) (het) | Bilateral renal cysts | |
| RGC-0101 | M | 16 | − | − | − | + | − | 1 | COL4A5 | arr[GRCh37]Xq22.3 (107868501–107869156)x0 (novel) | Alport syndrome | |
| RGC-0105 | F | 8 | − | + | − | + | − | 1 | COL4A4 | NM_000092.4: c.1334G>C (p.G445A) (het) and c.2570C>T (p.P857L) (het) | Steroid-sensitive nephrotic syndrome | |
| RGC-0108 | M | 15 | + | + | − | − | + | 1, 4 | OCRL | NM_000276.3: c.239delG (p.S80MfsX26) (hem) (novel) | Proteinuria | OCRL variant was maternally inherited |
| RGC-0110 | M | 5 | − | − | + | + | + | 5 | WDR19 | NM_025132: pathogenic c.1122_1123insT (p.P375fs) (het) (novel) and VUS c.817A>G (p.N273D) (het) | ESKD | Each variant in WDR19 is inherited from one parent |
| RGC-0112 | M | 14 | − | − | + | + | − | 2 | NPHP1 | arr[GRCh37]2q13 (110862477–110970270)x1 | CKD | |
| RGC-0113 | F | 6 | − | + | − | + | + | 2, 4 | PKD2 | NM_000297.3: c. 965G>A (p.R322Q) (het) | VUR, duplicated collecting system, and bilateral cystic kidney | PKD2 variant is paternally inherited |
| RGC-0115 | F | 7 | − | − | + | + | − | 1 | PKD2 | NM_000297.3: c.2614C>T (p.R872*) (het) | Unilateral renal cysts | |
| RGC-0116 | F | 1 | − | − | + | + | + | 1, 2, 5 | RPS19 | NM_001022: c.185G>A (p.R62Q) (het) | CKD and Diamond–Blackfan anemia | RPS19 variant is de novo |
| RGC-0117 | M | 0.16 | − | − | + | + | + | 2, 4 | BBS12 | NM_152618.2: pathogenic c.1115_1116delTT (p.F372*) (het), and VUS c.1277G>A (p.C426Y) (het) | Polydactyly and bilateral renal cysts | Each variant in BBS12 is inherited from one parent |
| RGC-0118 | M | 9 | + | + | − | + | + | 2, 4 | KCNJ1 | NM_000220.3: c.924C>A (p.C308*) (hom) | Renal dysplasia | Both parents are heterozygous for variant in KCNJ1 |
| RGC-0120 | M | 17 | − | − | − | + | + | 2, 4 | INVS | NM_014425.3: c.2695C>T (p.R899*) (hom) | Nephronophthisis | Both parents are heterozygous for variant in INVS |
| RGC-0124 | F | 17 | − | − | − | + | − | 1 | COL4A4 | NM_000092.4: c.1580del, (p.G527Vfs*126) (het) | Microscopic hematuria | |
| RGC-0128 | M | 2 | − | − | − | + | − | 1 | PKD1 | NM_01009944.2: c.8016+2T>C (IVS21+2T>C) (het) | Bilateral renal cysts | |
| RGC-0129 | M | 14 | − | − | − | − | + | 2, 4 | SLC7A9 | NM_014270.4: c.419T>C (p.F140S) (het) and c.164T>A (p.V55E) (het) (novel) | Cystine stones and dysplastic kidney | Each variant in SLC7A9 is inherited from one parent |
| RGC-0132 | F | 17 | − | − | + | + | − | 1 | PKD1 | NM_001009944.2: c.11712+1G>A (het) | Bilateral renal cysts | |
| RGC-0143 | M | 2 | + | − | + | − | + | 1 | NPHS1 | NM_004646.3; c.1747G>A (p.S910P) (het) (likely pathogenic), and c.1747G>A (p.E583K) (het) (VUS) | Nephrotic syndrome | Avoid immune suppression |
| RGC-0145 | M | 16 | − | + | − | − | + | 1 | NEK8 | NM_178170.2: c.1523T>A (p.Met508Lys) (het), and c.673G>C (p.Asp225His) (het) | Cystic kidney disease | Clinical diagnosis of ARPKD was changed to nephronophthisis |
| RGC-0147 | M | 14 | − | − | − | + | + | 2, 4 | KCNJ1 | NM_000220.3: c.924C>A, (p.C308*) (hom) | Bartter syndrome | Both parents are heterozygous for variant in KCNJ1 |
| RGC-0152 | F | 10 | − | − | + | + | − | 1 | COL4A5 | NM_000495.4: c.994_998delinsTCCC (p.Q332Sfs*14) (het) (novel) | Alport syndrome | |
| RGC-0156 | M | 14 | − | − | + | + | + | 1 | COL4A5 | NM_000495.4: c.4688+1G>T (hem) | Alport syndrome | COL4A5 variant is maternally inherited and sibling was tested negative for KFM |
| RGC-0157 | M | 12 | − | − | + | − | + | 1 | COL4A4 | NM_000092.4; c.1325G>C (p.G442A) (het) | Microscopic hematuria | |
| RGC-0159 | M | 2 | − | − | + | − | − | 1 | COL4A4 | NM_000092.4: c.1697–1G>A (het) | Microscopic hematuria | |
| RGC-0160 | M | 5 | − | − | + | − | + | 1 | AVPR2 | NM_000054.4: c.337C>T (p.R113W) (hem) | Diabetes insipidus | Subsequently sibling was tested positive for KFM |
| RGC-0162 | F | 8 | − | − | + | − | − | 1 | COL4A5 | NM_000495.4: c.2678G>A (p.G893D) (het) | Microscopic hematuria | |
| RGC-0164b | M | 1.3 | − | + | − | + | + | 4 | HNF1B | Arr[GRCh37]17q12 (34856055–36248918)x1dn | Bilateral renal cysts | This deletion is de novo and secondary finding of BRCA2 is maternally inherited |
| RGC-0171 | M | 2 | + | − | + | + | + | 2, 4 | WT1 | NM_024426.4: c.1432+4C>T (het) | Proteinuria, recurrent UTI, and hypospadias | WT1 variant was de novo |
| RGC-0182 | F | 11 | − | + | − | + | − | 1 | COL4A5 | NM_000495: c.557G>A (p.Gly186Asp) (het) (novel) | Microscopic hematuria | Familial diagnosis of FSGS changed to Alport syndrome |
| RGC-0183 | F | 16 | − | − | + | + | − | 1 | SLC12A3 | NM_000339; c.1001G>A (p.R334Q) (hom) | Gitelman syndrome | |
| RGC-0185 | F | 0.1 | + | − | + | − | − | 2, 5 | TPRM6 | NM_017662.4: c.5488–1G>C (hom) (novel) | Hypomagnesemia | Hypocalcemia and hypomagnesemia are due to defect in intestinal absorption of magnesium |
| RGC-0186 | M | 0.9 | + | − | − | + | − | 1 | WT1 | NM_0024426.3: c.1288C>T (p.R430*) (het) (novel) | Bilateral Wilms tumor | Impacted nephrectomy |
| RGC-0190 | F | 10 | + | − | + | + | + | 2, 4 | WT1 | NM_024426.4: c.1432+5 G>A (het) | ESKD and nephrotic range proteinuria | CMA revealed patient is XY female, and WT1 variant is de novo |
| RGC-0191 | F | 11 | + | − | + | − | − | 1 | CACNA1S | NM_000069.2: c.3715C>G (p.R1239G) (het) | Hypokalemia | Treatment with acetazolamide |
| RGC-0192 | M | 18 | − | + | − | + | + | 1, 2, 4 | COL4A5 | NM_000495.4: c.4298–20T>A (hem) (novel) | Hematuria and proteinuria | COL4A5 variant is maternally inherited |
L1, effect on medical and/or surgical treatment; L2, change of medical diagnosis; L3, providing diagnostic certainty; L4, subsequent evaluation of other body-system involvement; L5, cascade family member testing; SNV, single nucleotide variant; CNV, copy number variant; F, female; M, male; het, heterozygous; KFM, known familial mutation; hem, hemizygous; del, deletion; VUR, vesicoureteral reflux; HUS, hemolytic uremic syndrome; ins, insertion; hom, homozygous; ADPKD, autosomal dominant polycystic kidney disease; VUS, variant of uncertain significance; ARPKD, autosomal recessive polycystic kidney disease; ADHD, attention deficit hyperactivity disorder; PGF, paternal grandfather; UTI, urinary tract infection; CMA, chromosomal microarray.
a
Numbers represent the following testing types: 1, panel; 2, CMA; 3, proband exome sequencing; 4, trio exome sequencing; 5, Total BluePrint.
b
Patient had a secondray finding of pathogenic variant in BRCA2.