Table 1.
Seven different likely pathogenic heterozygous variants of FOXC1 in 8 families from a cohort of 550 CAKUT families.
| Family_individual | Genomic position | Transcript position | Amino acid change | Segregation | gnomAD (hom/het/WT allele count) | CADD | PPH2 | SIFT | MutationTaster | Mm | Gg | Xt | Dr | Ci | Ce | Dm | CAKUT phenotype | Extrarenal phenotype | Gender | Ethnicity |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A3938_21 | Chr6: g. 1610856G>T |
c.176G>T | p.Gly59Val | n/a | 0/0/Never reported | 25.1 | B: 0.304 | D:0.03 | DC:prob: 1 | S | G | G | G | G | A | Y | Bilateral renal hypodysplasia | Skeletal deformity, growth retardation | F | Indian |
| A3859_21 | Chr6: g. 1610893 1610898dup |
c.213_218 dup | p.Gln72_Pro73dup | n/a | 0/4/250048 | 22.3 | (Indel) | (Indel) | PUV, ESRD | Blindness, skeletal deformity, FTT | M | Indian | ||||||||
| B1252_21 | Chr6: g.1611113_161111 Bdel |
c.433_435 del | p.Lys145del | Maternal | 0/2/251376 | 22.4 | (Indel) | (Indel) | Left solitary kidney | Skeletal deformity, FTT, DD | M | Slavic American | ||||||||
| B1252_12 | n/a | (None specified) | High myopia, skeletal deformity, cerebral AVM | F | ||||||||||||||||
| B1402_21 | Chr6: g. 1611606_1611620del |
c.926_940 del | p.Ser309_Ile313del | Paternal | 0/1/89494 | 20.6 | (Indel) | (Indel) | Bilateral VUR | (None specified) | M | Romani | ||||||||
| B1402_11 | n/a | (None specified) | (None specified) | M | ||||||||||||||||
| A5071_31 | Chr6: g.1611705C>T |
c.1025C>T | p.Ala342Val | maternal | 0/2/66046 | 22.2 | B: 0.008 | T:0.13 | DC:prob: 0.712 | A | - | T | A | N | H | H | Prenatal left hydronephrosis (resolved at 2 years old) | (None specified) | M | Macedonian |
| A5071_22 | n/a | (None specified) | (None specified) | F | ||||||||||||||||
| B1830_21 | Chr6: g.1611770C>T |
c.1090C>T | p.Pro364Ser | n/a | 0/1/64716 | 19.23 | B:0.024 | T:0.39 | DC:prob: 1 | P | - | P | P | T | H | P | Left MCDK, right UPJO | (None specified) | F | Saudi Arabian |
| B2376_22 | Chr6: g.1611770C>T |
c.1090C>T | p.Pro364Ser | n/a | 0/1/64716 | 19.23 | B:0.024 | T:0.39 | DC:prob: 1 | P | - | P | P | T | H | P | PUV, bilateral VUR, CKD V left kidney stone | (None specified) | M | Saudi Arabian |
| A4451_21 | Chr6: g.1611819G>T |
c.1139G>T | p.Gly380Val | n/a | 0/0/Never reported | 16.45 | B:0.003 | D0 | DC:prob: 0.918 | G | - | - | - | - | - | S | VUR grade V | (None specified) | M | Macedonian |
Red background represents deleterious prediction by the in silico algorithm. Blue background represents tolerated prediction by the in silico algorithm. Green background represents the amino acid conservation. Black background represents indels. The genomic coordinates are based on genome build GRCh37 (hg19), and transcript NM_001453.2. All variants are heterozygous, and are located on the only exon of the transcript. AVM arteriovenous malformation, B benign, CADD combined annotation dependent depletion, CAKUT congenital anomalies of kidney and urinary tract, Ce Caenorhabditis elegans, Ci Ciona intestinalis, CKD chronic kidney disease, D deleterious, DC disease-causing, DD developmental delay, Dm Drosophila melanogaster, Dr Danio rerio, ESRD end-stage renal disease, FTT failure to thrive, Gg Gallus gallus, het heterozygous, hom homozygous, MCDK multicystic dysplastic kidney, Mm Mus musculus, PPH2 score PolyPhen-2 prediction score (0.0–1.0, i.e., tolerated to deleterious, variants from 0.85 to 1 are more confidently predicted to be damaging), PUV posterior urethral valve, SIFT sorting intolerant from tolerant, T tolerated, UPJO ureteropelvic junction obstruction, VUR vesicoureteral reflux, WT wild type, Xt Xenopus tropicalis.