Congenital Abnormalities of the Kidney and Urinary Tract (CAKUT) Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
2667 ACE 81479,81479 Order Options and Pricing
AGT 81479,81479
AGTR1 81479,81479
BMP4 81479,81479
BMP7 81479,81479
CDC5L 81479,81479
CHD1L 81479,81479
DSTYK 81479,81479
EYA1 81406,81405
FAT4 81479,81479
FGF20 81479,81479
FGFR2 81479,81479
FOXP1 81479,81479
FRAS1 81479,81479
FREM1 81479,81479
FREM2 81479,81479
GATA3 81479,81479
GLI2 81479,81479
GLI3 81479,81479
GREB1L 81479,81479
GRIP1 81479,81479
HNF1B 81405,81404
HOXA13 81479,81479
HOXA4 81479,81479
HOXB6 81479,81479
HPSE2 81479,81479
ITGA8 81479,81479
LIFR 81479,81479
LRP4 81479,81479
MUC1 81479,81479
NIPBL 81479,81479
NRIP1 81479,81479
PAX2 81406,81479
PBX1 81479,81479
REN 81479,81479
RET 81406,81479
ROBO1 81479,81479
ROBO2 81479,81479
SALL1 81479,81479
SIX1 81479,81479
SIX2 81479,81479
SIX5 81479,81479
SLIT2 81479,81479
SOX11 81479,81479
SOX17 81479,81479
SRGAP1 81479,81479
TBC1D1 81479,81479
TBX18 81479,81479
TRAP1 81479,81479
UMOD 81406,81479
UPK3A 81479,81479
VWA2 81479,81479
WNT4 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
2667Genes x (53)81479 81404, 81405, 81406, 81479 $990 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Congenital anomalies of kidney and urinary tract (CAKUT) represent a wide spectrum of structural malformations of the kidney and/or urinary tract due to defects during embryonic kidney development, accounting for 40-50% of children with chronic kidney disease worldwide (Sanna-Cherchi et al. 2018. PubMed ID: 29293093; Vivante et al. 2014. PubMed ID: 24398540; Nicolaou et al. 2015. PubMed ID: 26281895). The most common malformation is ureteropelvic junction obstruction (~20%). Other common clinical features within the CAKUT spectrum include renal agenesis, renal hypodysplasia, multicystic dysplastic kidney, hydronephrosis, megaureter, ureter duplex, vesicoureteral reflux (VUR), and posterior urethral valves. Age of onset of CAKUT varies from in utero to adulthood.

Genetics

CAKUT is a group of highly genetically and phenotypically heterogeneous diseases resulting from disturbances in normal nephrogenesis due to exposure to environmental risk factors or/and genetic defects (Sanna-Cherchi et al. 2018. PubMed ID: 29293093; Vivante et al. 2014. PubMed ID: 24398540; Nicolaou et al. 2015. PubMed ID: 26281895). Genetic diagnosis of CAKUT has been challenging due to genetic and phenotypic heterogeneity as well as incomplete genetic penetrance. Although studies suggest that the pathogenesis of the CAKUT spectrum is multifactorial (influenced by genetics, epigenetic and environmental factors), dozens of genes to date have been found to cause monogenic CAKUT; and copy number variations (CNVs) have been widely associated with CAKUT spectrum (Sanna-Cherchi et al. 2018. PubMed ID: 29293093). The implicated genes encode proteins in diverse developmental pathways. Inheritance modes of monogenic CAKUT include autosomal recessive (AR), autosomal dominant (AD) and X-linked (XL). The spectrum of pathogenic variants in causative genes includes all types of variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Overall, rare CNVs or single-nucleotide variants (SNVs) collectively explain at most 20% to 25% of CAKUT cases. Rates tend to be higher in patients with renal agenesis or hypodysplasia (RHD) (Sanna-Cherchi et al. 2018. PubMed ID: 29293093).

To date, HNF1B and PAX2 are the most frequent CAKUT-causing genes, accounting for about 5–15% of cases depending on the examined cohort (Vivante et al. 2014. PubMed ID: 24398540).

In a study of 62 families with CAKUT, pathogenic single-nucleotide variants (SNVs) in PAX2, HNF1B, and EYA1 were identified approximately 5% of families (Bekheirnia et al. 2017. PubMed ID: 27657687).

In a study of a total of 677 CAKUT patients and 301 patients with VACTERL association, Saisawat et al. identified TRAP1 recessive pathogenic variants in about 0.5% of the patients (Saisawat et al. 2014. PubMed ID: 24152966).

In a group of 311 patients with CAKUT, 7 (2.3%) were found to have heterozygous DSTYK pathogenic variants (Sanna-Cherchi et al. 2013. PubMed ID: 23862974).

Next generation sequencing panel testing for patients with CAKUT demonstrated that <10% patients with isolated CAKUT carry variants in genes such as HNF1B, PAX2, EYA1, SIX5, and RET (Nicolaou et al. 2015. PubMed ID: 26281895).

In 5 out of 590 families (2.5%) affected by isolated CAKUT, recessive pathogenic variants were identified in the Fraser syndrome-related genes FRAS1, FREM2, GRIP1, FREM1, ITGA8, and GREM1 (Kohl et al. 2014. PubMed ID: 24700879).

In a study of 183 unrelated families affected by CAKUT, 16 (8.7%) heterozygous pathogenic or suspected pathogenic variants in GREB1L were identified, 12 of which were found in 54 cases (25.8%) with bilateral kidney agenesis in this cohort (De Tomasi et al. 2017. PubMed ID: 29100091). In another study of 612 individuals affected by renal agenesis and hypodysplasia (RHD), 17 (2.8%) heterozygous pathogenic or suspected pathogenic variants in GREB1L were identified (Sanna-Cherchi et al. 2017. PubMed ID: 29100090).

For many genes of this panel, due to high genetic and phenotypic heterogeneity, pathogenic variant detection rate of each individual gene in a larger cohort of patients with CAKUT relevant phenotypes is unavailable.

At this time, the clinical sensitivity of deletion/duplication testing is difficult to estimate due to the lack of large cohort studies. However, copy number variations of large size (beyond a gene-centric scale) have been indicated to be a common cause of the CAKUT spectrum. For example, in a study involving 522 patients with CAKUT, 72 distinct known or novel copy-number variations in 87 (16.6 %) patients were identified (Sanna-Cherchi et al. 2012. PubMed ID: 23159250).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.7% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

To date, the only documented pathogenic variant in MUC1 causing medullary cystic kidney disease is the insertion of a single cytosine in one copy of the repeat unit comprising the extremely long (∼1.5-5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence (Kirby et al. 2013). Our current sequencing methodology has not been validated to detect this variant.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with the CAKUT spectrum. This test especially aids in a differential diagnosis of similar phenotypes by analyzing multiple genes simultaneously.

Diseases

Name Inheritance OMIM ID
Apert Syndrome AD 101200
Barakat Syndrome AD 146255
Branchiootic Syndrome 3 AD 608389
Branchiootorenal Syndrome 1, with or without Cataracts AD 113650
Branchiootorenal Syndrome 2 AD 610896
Congenital Anomalies of Kidney and Urinary Tract 2 AD 143400
Congenital anomalies of kidney and urinary tract 3 AD 618270
Congenital Anomalies of Kidney and Urinary Tract Syndrome with or without Hearing Loss, Abnormal Ears, or Developmental Delay AD 617641
Congenital Anomalies of Kidney and Urinary Tract, Susceptibility to AD 610805
Cornelia de Lange syndrome 1 AD 122470
Familial Juvenile Hyperuricemic Nephropathy AD 162000
Fraser Syndrome AR 219000
Glomerulosclerosis, Focal Segmental, 7 AD 616002
Greig Cephalopolysyndactyly Syndrome AD 175700
Hand Foot Uterus Syndrome AD 140000
Holoprosencephaly 9 AD 610829
Manitoba Oculotrichoanal Syndrome AR 248450
Maturity-Onset Diabetes Of The Young, Type 5 AD 137920
Medullary Cystic Kidney Disease 1 AD 174000
Mental Retardation With Language Impairment And Autistic Features AD 613670
Mental Retardation, Autosomal Dominant, 27 AD 615866
Microphthalmia Syndromic 6 AD 607932
Mullerian Aplasia And Hyperandrogenism AD 158330
Pallister-Hall Syndrome AD 146510
Papillorenal Syndrome AD 120330
Polydactyly Preaxial Type 4 AD 174700
Polydactyly, Postaxial, Type A1 AD 174200
Preaxial Deficiency, Postaxial Polydactyly And Hypospadias AD 176305
Renal Adysplasia AR 191830
Renal Hypodysplasia/Aplasia 2 AR 615721
Renal Hypodysplasia/Aplasia 3 AD 617805
Renal Tubular Dysgenesis AR 267430
Stuve-Wiedemann Syndrome AR 601559
Syndactyly Cenani Lenz Type AR 212780
Thyroid Cancer, Follicular AD 188470
Townes-Brocks Syndrome AD 107480
Urofacial Syndrome 1 AR 236730
Van Maldergem Syndrome 2 AR 615546
Vesicoureteral Reflux 2 AD 610878
Vesicoureteral Reflux 3 AD 613674

Related Test

Name
PGxome®

Citations

  • Bekheirnia et al. 2017. PubMed ID: 27657687
  • De Tomasi et al. 2017. PubMed ID: 29100091
  • Kohl et al. 2014. PubMed ID: 24700879
  • Nicolaou et al. 2015. PubMed ID: 26281895
  • Saisawat et al. 2014. PubMed ID: 24152966
  • Sanna-Cherchi et al. 2012. PubMed ID: 23159250
  • Sanna-Cherchi et al. 2013. PubMed ID: 23862974
  • Sanna-Cherchi et al. 2017. PubMed ID: 29100090
  • Sanna-Cherchi et al. 2018. PubMed ID: 29293093
  • Vivante et al. 2014. PubMed ID: 24398540

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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