Saethre-Chotzen Syndrome: TWIST1 Deletion/Duplication MLPA

Clinical Information

Saethre-Chotzen Syndrome is one of the most common autosomal dominant disorders of craniosynostosis, affecting approximately 1/2000 newborn infants. It is characterized by craniofacial and limb anomalies. variants in the TWIST1 gene, which maps to chromosome 7p21-p22 are found in a majority of individuals with Saethre-Chotzen syndrome. Nonsense, missense, insertion, and deletion variants of the TWIST1 gene have been found in studies of patients with Saethre-Chotzen syndrome.

Technical Information

• This test is performed using Multiplex Ligation-dependent Probe Amplification (MLPA).
• MLPA analysis is performed to determine if deletions or duplications involving the TWIST1 gene are present. MLPA identifies copy number changes of specific genomic sequences (Shouten et al., 2002, Nucleic Acids Research 30, 12e57).
• The Craniofacial MLPA kit used for this test measures the dosage of several genes including TWIST1 (i.e., FGFR1, FGFR2, FGFR3, TWIST1, MSX2, ALX1, ALX3, ALX4, EFNB1 and RUNX2). Probes for exons 1 and 2 of the TWIST1 gene and exon 4 of TWISTNB gene (TWIST nearby, located 500 kb from TWIST1) are analyzed and quantified along with control probes.

Specimen Requirements

• The preferred sample type is 3-4 ml of peripheral blood collected in an EDTA (purple top) tube. Blood kits are available by request.
• DNA is also accepted for this test. Send approximately 5µg of extracted DNA at a requested concentration of 90-130 ng/µl.

Transport Instructions

• The blood specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.
• Extracted DNA should be sent at room temperature via overnight delivery.