skip to content »

Pediatrics - Cardiology

Houston, Texas

BCM faculty, staff and trainees are the heart of the organization.
Pediatrics - Cardiology
not shown on screen

SMAD8 Mutation Analysis

SMAD8, also known as SMAD9, is one of the receptor-regulated SMADs (R-SMADs) for the TGF-β superfamily of receptors. The SMAD proteins are homologs of both the drosophila protein mothers against decapentaplegic (MAD) and the C. elegans protein SMA, so it's named. SMAD8, SMAD1 and SMAD5 are direct substrates of TGF-β/BMP type I receptor kinase and are phosphorylated at the SXS motif in the C-terminal region. Activated SMAD8 then associates with Co-SMAD SMAD4 and translocates into the nucleus, where they regulate the transcription of target genes. SMAD8 gene contains five exons spanning over 75kb of genomic distance that was mapped to chromosome 13q12-q14. Mutations in SMAD8 gene are associated with primary pulmonary hypertension 1 (PPH1) and pulmonary arterial hypertension (PAH).

The John Welsh Cardiovascular Diagnostic Laboratory offers molecular genetic testing for SMAD8 mutations. Individuals are tested by automatic fluorescent DNA sequencing of the coding exons of the SMAD8 gene. We strongly recommend initial testing of a clearly affected individual, if available, in order to provide the greatest test sensitivity and clearest interpretation of results for subsequent family members. Genetic counseling is recommended for all individuals.

Reasons for Referral

Molecular confirmation of the diagnosis of pulmonary arterial hypertension (PAH).


Genomic DNA is analyzed for SMAD8 mutations by automatic fluorescent DNA sequencing of the coding exons of the SMAD8 gene, as well as the exon/intron junctions and a portion of the 3` untranslated region. Patient DNA is sequenced in both the forward and reverse orientations. If a mutation is identified, additional family members are analyzed only for the familial mutation by automatic fluorescent DNA sequencing.

Service Fees

Service Direct and Institutional Billing CPT Codes
Index Case (Male or Female) $500 per sample 81404, G0452
Additional Family Members $300 per sample; known familial mutation only 81403, G0452


DNA Sequencing Analysis: Approximately 99 percent detection of mutations in the coding exons of SMAD8

Specimen Requirements

Blood (preferred): EDTA (purple-top) tubes: Adult: 5 cc, Child: 5 cc, Infant: 2-3 cc
Tissue: Frozen (preferred), RNAlater, Formalin-fixed, Paraffin-embedded
Other Body Fluids: Call to inquire
Buccal Swabs: One swab from each cheek

Download Printable PDF

E-mail this page to a friend