ROTHMUND-THOMSON SYNDROME (RTS)
RECQL4 Sequencing
DNA ANALYSIS

Rothmund–Thomson syndrome (RTS) is an autosomal recessive disorder associated with an increased predisposition to osteosarcoma. Children with RTS typically present with a characteristic skin rash (poikiloderma), small stature, cataracts and skeletal dysplasias. Clinical features may vary in RTS patients, and a conclusive laboratory test for this disorder was not previously available on a clinical basis. Approximately two thirds of patients with RTS carry mutations in the RECQL4 gene on chromosome 8q24.3. The other gene(s) responsible for RTS have not yet been identified. The RECQL4 gene encodes a protein that belongs to the RecQ family of DNA helicases, which includes gene products that are disrupted in Bloom syndrome and Werner syndrome, two clinically related cancer predisposition syndromes. DNA helicases are enzymes that unwind DNA and are involved in many basic cellular processes; interruption of helicase functions may reduce genomic stability and thus contribute to tumorigenesis. RTS with osteosarcoma is associated with RECQL4 loss-of-function mutations. Genotype-Phenotype correlations have been described by Wang et al (2002). Sequence analysis of the entire RECQL4 gene associated with RTS is available on a clinical basis at the Medical Genetics Laboratories at Baylor College of Medicine.

Reasons for Referral:

Confirmation of clinical diagnosis of RTS.
Analysis of at-risk family members for identified mutations. (Population carrier screening not offered)
Prenatal diagnosis (Known mutation only)

Testing Methodology:

PCR amplification of 21 exons and introns contained in the RECQL4 gene will performed on patient genomic DNA. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Sensitivity:

Clinical: Approximately 66%
Analytical: Approximately > 98%

Specimen Requirements:

Blood: EDTA (purple-top) tubes Adult/Child: Minimum 6-14 cc.
Requisition form must accompany the specimen. Prior to any genetic testing, we recommend genetic counseling and we request that the subject sign our consent statement and submit it with the sample. To receive forms, additional information or specimen collection kits, please contact the laboratory.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 3 weeks

Additional Information:

Additional Family Members-Known familial mutation only. Prenatal Testing-Known familial mutation only. Please call Laboratory for specific requirements for prenatal testing.

CPT Codes and Prices:

Index: 83904x22, 83912, 83909x44, 83898x11, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Kitao, et al. (1999) Nat. Genet. 22: 82-84.
2. Wang, et al. (2003) J. Natl. Cancer. Inst. 95: 669-674.
3. Wang, et al. (2002) Am. J. Hum. Genet. 71: 165-167.

Shipping Information

Forms:

>> Cancer DNA Requisition
>> Prenatal Requisition

Test Codes:

Index: 6121
Known Familial Mutation: 6122
Prenatal (Known Familial Mutation Only): 6112