Isolated Nonsyndromic Congenital Heart Defects via the GATA4 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9993 GATA4 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9993GATA481479 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Congenital heart defects (CHDs) are the most common birth defect, occurring in 6-10 of every 1000 live births and are a major cause of infant morbidity and mortality (Hoffman and Kaplan J Am Coll Cardiol 39:1890-1900, 2002; Oyen et al. Circulation 120:295-301, 2009). Congenital heart diseases arise due to defects in cardiac morphogenesis during embryonic development, which leads to structural malformations in the heart and great vessels. Cardiac septal defects, which include atrial septal defects (ASD), ventricular septal defects (VSD), and atrioventricular septal defects (AVSD), are common, with an estimated incidence of 5 in 1000 live births (Wessels et al. Clin Genet 78:103-123, 2010).

Genetics

CHDs have genetic and non-genetic causes. The majority of patients with CHDs are thought to have a complex, multifactorial etiology. CHDs can be caused by single gene or chromosomal abnormalities, exposure to teratogens, and other unknown mechanisms. Non-cardiac malformations are found in roughly one-fifth of patients with CHD, and chromosomal abnormalities account for ~7% of patients with CHDs (Eskedal et al. Cardiol Young 14:600-607, 2004; Oyen et al. Circulation 120:295-301, 2009). Monogenic non-syndromic CHDs are caused by variants in regulators of heart development (reviewed by Bruneau Nature 451:943-948, 2008). Atrial septal defect 2 (ASD2; OMIM 607941) is inherited as an autosomal dominant trait caused by variants in the zinc finger DNA binding protein GATA4. Variants in GATA4 have been reported in familial and sporadic cases of cardiac septal defects (ASD, VSD, and AVSD) with and without conotruncal defects, such as tetralogy of Fallot (TOF; Garg et al. Nature 424:443-447, 2003; Nemer et al. Hum Mutat 27:293-294, 2006; Tomita-Mitchell et al. J Med Genet 44:779-783, 2007; Moskowitz et al. PNAS 108:4006-4011, 2011). The majority of documented causative variants in GATA4 are missense variants; however, nonsense, small insertions, and small deletions have also been reported. In addition to congenital heart diseases, missense variants in GATA4 have also been found in patients with lone atrial fibrillation (Posch et al. Eur J Med Genet 53:201-203, 2010) and in 46, XY disorders of sexual development (Lourenco et al. PNAS 108:1597-1602, 2011).

Testing Strategy

This test provides full coverage of all coding exons of the GATA4 gene 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 full coverage as >20X NGS reads or Sanger sequencing.

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

Clinical Sensitivity - Sequencing with CNV PGxome

Variants in the GATA4 gene have been reported in 1-2% of patients with sporadic cases of ASD, VSD, AVSD, and in less than 1% of patients with conotruncal defects (Tomita-Mitchell et al. J Med Genet 44:779-783, 2007; Zhang et al. Eur J Med Genet 51:527-535, 2008; Moskowitz et al. PNAS 108:4006-4011, 2011).

Indications for Test

Patients with non-syndromic CHDs, including cardiac septal defects (ASD, VSD, AVSD) or TOF, are candidates for this test.

Gene

Official Gene Symbol OMIM ID
GATA4 600576
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Øyen N, Poulsen G, Boyd HA, Wohlfahrt J, Jensen PK, Melbye M. (2007) Recurrence of congenital heart defects in families. Circulation 120(4):295-301. PubMed ID: 19597048
  • Øyen N, Poulsen G, Boyd HA, Wohlfahrt J, Jensen PK, Melbye M. (2009) Recurrence of congenital heart defects in families. Circulation 120(4):295-301. PubMed ID: 19597048
  • Bruneau. (2008) The developmental genetics of congenital heart disease. Nature 451(7181):943-948. PubMed ID: 18288184
  • Eskedal L, Hagemo P, Eskild A, Aamodt G, Seiler KS, Thaulow E. (2004) A population-based study of extra-cardiac anomalies in children with congenital cardiac malformations. Cardiol Young 14(6):600-607. PubMed ID: 15679995
  • Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, Rothrock CR, Eapen RS, Hirayama-Yamada K, Joo K, Matsuoka R, Cohen JC, Srivastava D. (2003) GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature 424(6947):443-447. PubMed ID: 12845333
  • Hoffman JI, Kaplan S. (2002) The incidence of congenital heart disease. J Am Coll Cardiol 39(12):1890-900. PubMed ID: 12084585
  • Lourenço D, Brauner R, Rybczynska M, Nihoul-Fékété C, McElreavey K, Bashamboo A. (2011) Loss-of-function mutation in GATA4 causes anomalies of human testicular development. PNAS 108(4):1597-1602. PubMed ID: 21220346
  • Moskowitz IP, Wang J, Peterson MA, Pu WT, Mackinnon AC, Oxburgh L, Chu GC, Sarkar M, Berul C, Smoot L, Robertson EJ, Schwartz R, Seidman JG, Seidman CE. (2011) Transcription factor genes Smad4 and Gata4 cooperatively regulate cardiac valve development.  PNAS 108(10):4006-4011. PubMed ID: 21330551
  • Moskowitz IP, Wang J, Peterson MA, Pu WT, Mackinnon AC, Oxburgh L, Chu GC, Sarkar M, Berul C, Smoot L, Robertson EJ, Schwartz R, Seidman JG, Seidman CE. (2011) Transcription factor genes Smad4 and Gata4 cooperatively regulate cardiac valve development.  PNAS 108(10):4006-4011. PubMed ID: 21330551
  • Nemer G, Fadlalah F, Usta J, Nemer M, Dbaibo G, Obeid M, Bitar F. (2006) A novel mutation in the GATA4 gene in patients with Tetralogy of Fallot. Hum Mutat 27(3):293-294. PubMed ID: 16470721
  • Posch MG, Boldt LH, Polotzki M, Richter S, Rolf S, Perrot A, Dietz R, Ozcelik C, Haverkamp W. (2010) Mutations in the cardiac transcription factor GATA4 in patients with lone atrial fibrillation. Eur J Med Genet 53(4):201-203. PubMed ID: 20363377
  • Tomita-Mitchell A, Maslen CL, Morris CD, Garg V, Goldmuntz E. (2007) GATA4 sequence variants in patients with congenital heart disease. J Med Genet 44(12):779-783. PubMed ID: 18055909
  • Tomita-Mitchell A, Maslen CL, Morris CD, Garg V, Goldmuntz E. (2007) GATA4 sequence variants in patients with congenital heart disease. J Med Genet 44(12):779-783. PubMed ID: 18055909
  • Wessels MW, Willems PJ. (2010) Genetic factors in non-syndromic congenital heart malformations. Clin Genet 78(2):103-23. PubMed ID: 20497191
  • Zhang W, Li X, Shen A, Jiao W, Guan X, Li Z. (2008) GATA4 mutations in 486 Chinese patients with congenital heart disease. Eur J Med Genet 51(6):527-535. PubMed ID: 18672102

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

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