Table 1.
Identification of six different X-linked recessive variants in the gene ARHGEF6 (NM_004840.3) in eight male individuals with CAKUT
| Family Individual | Self-Reported Ethnicity, Race, or Origin | Con-san-guinity | Nucleotide Change AA Change | hg19 Position | Exon (Segregation) Zygostiy | PP2/SIFT/MT | CADD/REVEL | AA Conservation | gnomAD Allele Frequencies (hom/hemi/het/Total Count) | Renal Phenotype | Extrarenal Features |
|---|---|---|---|---|---|---|---|---|---|---|---|
| GM1 | White | No | c.571C>T p.Arg191* | chrX: 135825834 | 5 (m), hemi | NA | NA | NA | NP | Bilateral renal agenesis | CM, termination of pregnancy at 21 wk |
| B3089-21 | Mace donia | No | c.833G>A p.Ser278Asn | chrX: 135790924 | 8 (m), hemi | 0.36/Del/Dis | 20.3/0.092 | D.m. | 0/7/19/204,748 | Hypoplastic kidney with VUR IV-V ri, VUR II le | — |
| B1185-21 | White | No | c.1158_ 1159del p.Leu387 Alafs*58 |
chrX: 135772799_135772800 | 10, hemi | NA | NA | NA | NP | Bladder exstrophy with VUR I le, II-III ri, medullary nephrocalcinosis, hypospadias | Kyphosis, extra vertebrate, attention deficit disorder |
| A5124 -11 -32 -33 |
Ashkenazi | No | c.1331T>A p.Ile444Asn | chrX: 135767897 | 12 (m), hemi | 0.94/Del/Dis | 23.1/0.44 | X.t. | 0/4/10/183,437 | 11: renal hypoplasia le 32: renal hypoplasia le, bladder diverticula 33: renal hypoplasia ri |
-11: Deafness |
| KMC1 | Ashkenazi/Russian nonjewish | No | c.1549delG p.Glu517 Lysfs*27 |
chrX: 135764058 | 14, hemi | NA | NA | NA | NP | Unilateral renal agenesis ri | Autism, sleeping disturbances recurrent vomiting |
| GM2 | African American | No | c.2135+4 A>G p.? |
chrX: 135754175 | i20 (m), hemi | NA | NA | NA | 0/0/4/205,321 | Bilateral hydrouretero-nephrosis, VUR grade V le, hypodysplastic le kidney, PUV (ablated), trabeculated bladder. | — |
AA, amino acid change; PP2, Polyphen Prediction score Humvar; SIFT Sorting Intolerant From Tolerant; MT, mutationtaster; CADD, Combined Annotation Dependent Depletion; REVEL, Rare Exome Variant Ensemble Learner; hom, homozygous; hemi, hemizygous; het, heterozygous; NA, not applicable; NP, not present; CM, cardiomyopathy; Del, deleterious; Dis, disease causing; D.m., Drosophila melanogaster; VUR, vesicoureteral reflux; ri, right; le, left; X.t., Xenopus tropicalis; m, mother; M, male; PUV, posterior urethral valves.