Table 4 Clinical and genetic details of children with a positive genetic diagnosis
From: Clinical utility of genetic testing in Indian children with kidney diseases
Case | Age mo | Sex | Family history of similar illness | Disease category | Clinical diagnosis | Gene | Location | Variant | Zygosity | ACMG Classification | Genetic diagnosis (AD/AR/XL) | Utility of genetic testing |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 24 | F | No | 5 | Bardet Biedl Syndrome | CEP164 | Exon 23 | c.2863G > T p.Glu955Ter | Homo | Pathogenic | Nephronopthisis 15 (AR) | New diagnosis |
2 | 5 | F | No | 3 | Primary Hyperoxaluria | AGXT | exon2 | c.245G > A p.Gly82Glu | Homo | Pathogenic | PH-1 (AR) | Confirmed the diagnosis and diagnosed the exact type of PH |
4 | 10 | M | No | 3 | Primary Hyperoxaluria | AGXT | Exon1 | c.32C > G, c.107G > A p.Pro11Arg, p.Arg36His | Homo Homo | Pathogenic | PH-1 (AR) | Confirmed the diagnosis and diagnosed exact type of PH, Fetus in subsequent pregnancy aborted after the same mutation detected in the fetus |
5 | 96 | M | No | 2 | FSGS rapidly progressed to ESRD, Pre-transplant evaluation for disease recurrence | NPHP1 | Exon 1–20 | Deletion of the region | Homo | Likely pathogenic | Nephronophthisis 1 (AR) | New diagnosis, changed the diagnosis from FSGS to ciliopathy, clarified disease recurrence risk post-transplant |
7 | 4 | F | No | 1 | RTA | ATP6V0A4 | Exon 13 | c.1185del p.Tyr396ThrfsTer12 | Homo | Pathogenic | d RTA with preserved hearing (AR) | Confirmed the diagnosis and led to finding other features like SNHL |
12 | 10 | M | No | 3 | Hyperuricemic nephrolithiasis | HPRT1 | Exon 3 | c.212dupG p.Tyr72LeufsTer2 | Hemi | Pathogenic | Lesch nyhan syndrome (XLR) | New diagnosis |
13 | 10 | F | No | 1 | RTA | SLC4A1 | Exon 19 | c.2573C > A p.Ala858Asp | Homo | pathogenic | d RTA (AR) | Confirmed the diagnosis |
14 | 1 | M | No | 3 | Uric acid stone, Hyperuricemia | HPRT1 | intron 1 | c.27 + 2 T > G 5 slice error | Hemi | Pathogenic | Lesch nyhan syndrome (XLR) | Diagnostic, new diagnosis, second issue fetus same mutation, aborted |
16 | 120 | F | No | 6 | Nephronopthisis | NPHP1 | Deletion probable | chr2:g.(?-109,974,999)-110,213,122-?del | Homo | Likely Pathogenic | Nephronopthisis1, Joubert, SLS (AR) | Diagnostic and confirmatory |
21 | 1 | M | No | 1 | Bartter syndrome | SLC12A1 | Exon22 | c.2716C > T p.Gln906Ter | Homo | Pathogenic | bartter syndrome 1 (AR) | Diagnostic and confirmatory |
22 | 4 | M | No | 3 | Primary Hyperoxaluria | AGXT | Exon2 | c.245G > A p.Gly82Glu | Homo | Pathogenic | PH-1 (AR) | Confirmatory and disease classification |
24 | 22 | F | No | 2 | Primary SRNS, FSGS | LAMB2 | Exon29, 9 | c.4882dup, c.1045 T > A p.Ala1628GlyfsTer4, p.Cys349Ser | Compound Hetero | Pathogenic | Pierson syndrome (AR) | New diagnosis |
27 | 12 | F | No | 3 | Nephrolithiasis | HOGA1 | Exon1 | c.134C > T p.Pro45Leu | Homo | Likely pathogenic | PH-3 (AR) | New diagnosis and disease classification |
29 | 24 | M | Yes | 2 | Primary SRNS | PLCE1 | Exon 20 | c.4848del p.Gln1616HisfsTer12 | Homo | Pathogenic | DMS NS 3 (AR) | Diagnostic |
30 | 47 | F | No | 1 | Proximal RTA | FAH | Exon3 | c.192G > T p.Gln64His | homo | Pathogenic | Tyrosinemia type 1 (AR) | New diagnosis |
31 | 6 | F | No | 3 | Primary Hyperoxaluria | AGXT | Exon 2 | c.302 T > C p.Leu101Pro | Homo | Pathogenic | PH-1 (AR) | Confirmatory and disease classification |
32 | 96 | F | No | 5 | Nephronopthisis | DYNC2H1 | Exon 65, Intron 30 | c.9844C > T, c.4612-4A > G p.Arg3282Ter | Compound Hetero | Pathogenic | Short Rib Thoracic Dysplasia 3 with or without polydactyly | New diagnosis |
34 | 1 | M | No | 1 | Nephropathic cystinosis | CTNS1 | Exon7 | c.461G > T p.Ser154Ile | Homo | Pathogenic | Nephropathic cystinosis | Confirmatory |
35 | 105 | F | No | 6 | CKD of unknown aetiology | COL4A4 | Exon 47 | c.4717del p.Ala1573ProfsTer30 | Homo | Pathogenic | Alport syndrome (AR) | New diagnosis. Led to reverse phenotyping and detecting the same variation in the younger brother who had hematuria |
37 | 24 | M | No | 2 | Frasier/Denys Drash Syndrome | WT1 | Exon 4 | c.896C > T Pp.Ser299Phe | Hetero | Likely pathogenic | Denys Drash Syndrome (AD) | Diagnostic, got a genetic diagnosis after 12 years |
38 | 96 | F | No | 8 | Primary hypoparathyroidism | AIRE | Exon2, 2 | c.165del, c.195G > T p.Gln57ArgfsTer11,p.Trp65Cys | Compound Hetero | Pathogenic | Autoimmune PES type 1 (AR) | New diagnosis |
42 | 24 | F | No | 1 | Hypophosphatemic rickets | PHEX | Exon15 | c.1645C > T p.Arg549Ter | Hetero | Pathogenic | XLHR | Confirmatory |
44 | 120 | M | No | 6 | CKD of unknown etiology | COL4A5 | Exon 15 | c.884G > A p.Gly295Asp | Hemizygous | Pathogenic | XLAS | New diagnosis |
48 | 4 | M | No | 1 | Fanconi syndrome | SLCA2 | Exon3 | c.339del p.Phe114LeufsTer16 | Homo | Pathogenic | Fanconi Bickel Syndrome (AR) | New diagnosis, Diagnostic and avoided liver biopsy |
49 | 0 | M | No | 5 | ARPKD | PKHD1 | Exon 54,65 | c.8501dup,c.11542G > C p.Val2836SerfsTer4,p.Val3848Leu | Compound Hetero | Pathogenic | ARPKD | confirmatory |
51 | 60 | M | No | 2 | Primary SRNS, FSGS | COL4A3 | Exon 3 | c.172_178dup p.Pro60ArgfsTer12 | Homo | Pathogenic | FSGS COL4A3 (AR) | Diagnostic, new diagnosis |
57 | 120 | M | Yes | 9 | Alport syndrome | COL4A5 | Exon 44 | c.3850G > T p.Gly1284Ter | Hemi | Pathogenic | XLAS | Confirmatory |
59 | 120 | M | No | 5 | Nephronopthisis SLS | SDCCAG8 | Exon 16 | c.1885dup p.Arg629LysfsTer5 | Homo | Pathogenic | SLS (AR) | Diagnostic, stopped immunosuppression which was previously started thinking chronic glomerulonephritis |
63 | 16 | F | No | 2 | Primary SRNS | NPHS2 | Exon 3 | c.412C > T p.Arg138Ter | Homo | Pathogenic | FSGS Podocin mutation (AR) | Diagnostic |
66 | 119 | F | No | 9 | Alport Syndrome | COL4A3 | Exon 22 | c.1343delC p.Pro448LeufsTer10 | Homo | Pathogenic | ARAS | Confirmatory |
67 | 48 | F | No | 2 | Primary SRNS/FSGS | WT1 | intron9 | c.1432 + 5G > A(5' proximal site) p.Pro739Ala | Hetero | Pathogenic | Frasier syndrome (AD) | New diagnosis. Reverse phenotyping revealed complete sex reversal on karyotyping |
70 | 132 | F | No | 3 | Primary Hyperoxaluria | KCNJ1 | Exon2 | c.658C > T p.Leu220Phe | Homo | Likely Pathogenic | Bartter syndrome type 2 (AR) | New diagnosis. Reverse phenotyping indeed revealed Bartter syndrome on investigation |
71 | 170 | M | No | 3 | Primary Hyperoxaluria | AGXT | Exon 1,5 | c.33dupC, c.577dupC p.Lys12GlnfsTer156,p.Leu193ProfsTer32 | Compound Hetero | Pathogenic | PH-1 (AR) | Confirmatory |
72 | 192 | F | No | 5 | ADPKD | PKHD1 | Exon3, Intron 5 | c.4870C > T C.390 + 5G > T p.Arg1624Trp 5 slice site | Compound Hetero | Likely pathogenic | ARPKD | Changed the diagnosis |
76 | 60 | F | No | 9 | Alport syndrome | COL4A4 | Exon 47 | c.4717del; p.Ala1573ProfsTer30 | Homo | Pathogenic | ARAS | Confirmatory |