SCHMID METAPHYSEAL CHONDRODYSPLASIA (SMCD)
COL10A1 Sequencing
DNA ANALYSIS

Schmid Metaphyseal Chondrodysplasia (SMCD; MIM# 156500) is an autosomal dominant skeletal dysplasia characterized by short-limbed short stature with normal facies and intelligence, coxa vara, genu varum, and a waddling gait. Irregularities of the metaphyseal ends of bones of the extremities are demonstrated radiologically. These radiographic features include flaring of metaphyses and irregular, wide growth plates in the short and long tubular bones. SMCD is caused by mutations in the COL10A1 gene for collagen X, a short-chain collagen expressed by hypertrophic chondrocytes in the growth plate during endochondral ossification. Mutation of COL10A1 has also been reported in one Japanese family diagnosed with Spondylometaphyseal Dysplasia, a skeletal dysplasia overlapping with SMCD but also showing spine dysplasias. Sequence analysis of the entire COL10A1 gene associated with Schmid Metaphyseal Chondrodysplasia is available on a clinical basis at the Medical Genetics Laboratories at Baylor College of Medicine.

Reasons for Referral:

Confirmation of clinical diagnosis of Schmid Metaphyseal Chondrodysplasia.
Prenatal diagnosis (known mutation only).

Testing Methodology:

Full Sequencing: A PCR-based assay is used to amplify all 3 exons of the COL1OA1 gene. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Sensitivity:

Clinical: Approximately 80%
Analytical: > 98%

Specimen Requirements:

Blood for DNA: 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. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 3 weeks

CPT Codes and Prices:

Index: 83904x12, 83912, 83909x12, 83898x6, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Bateman JF, et al. (2004) Identification of four novel COL10A1 missense mutations in Schmid Metaphyseal Chondrodysplasia: further evidence that collagen X NC1 mutations impair trimer assembly. Hum. Mutat. 23: 396.
2. Ikegawa S, et al. (1998) Mutation of the type X collagen gene (COL10A1) causes Spondylometaphyseal Dysplasia. Am. J. Hum. Genet. 63: 1659-1662.
3. Elliott, AM, Field FM, Rimion DL, Lachman RS. (2005) Hand involvement in Schmid metaphyseal chondrodysplasia. Am. J. Med. Genet. 132A: 191-193.

Shipping Information

Forms:

>>Gene Sequencing Requisition
>> Prenatal Requisition

Test Codes:

Index: 6285
Known Familial Mutation:6290
Prenatal (Known Familial Mutation Only): 6295