CARTILAGE HAIR HYPOPLASIA (CHH)
RMRP Sequencing
DNA ANALYSIS

Cartilage Hair Hypoplasia (CHH; MIM # 250250) is a rare autosomal recessive skeletal disorder characterized by metaphyseal dysplasia in the long and/or short tubular bones. The phenotype is remarkably pleiotropic even within families. The most common presentation is short-limbed short stature. Other common features include fine, sparse, light-colored hair, incomplete extension at the elbows, anterolateral chest deformity, genu varum, and long fibula relative to the tibia. The fingers are usually loose-jointed and with foreshortened fingernails. The hematopoietic system may show lymphopenia leading to defective immunity; neutropenia and hypoplastic anemia may also be present. There is an increased risk of lymphoma and other malignancies. The intestines show neuronal dysplasia, which in severe cases may be associated with congenital megacolon (Hirschsprung’s disease). CHH is frequent among the Amish (carrier frequency 1:19) and Finns (carrier frequency 1:76), but occurs in numerous other populations. The locus for CHH is chromosome 9p13, which contains the untranslated RMRP gene that encodes the structural RNA component of a ribonucleoprotein endoribonuclease. Numerous mutations and polymorphisms have been described. The major mutation of RMRP in CHH (70A>G) has also been identified in patients with Schmid Metaphyseal Chondrodysplasia that lack mutations in COL10A1.

Reasons for Referral:

Confirmation of clinical diagnosis of Cartilage Hair Hypoplasia.
Prenatal testing for known familial mutation.
Assessment of carriers in high risk family members – known mutation analysis.
Evaluation for metaphyseal chondrodysplasia.

Testing Methodology:

Full Sequencing: PCR amplification of one exon contained in the RMRP gene coding region is 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 .

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. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

4 weeks

CPT Codes and Prices:

Index: 83904X25, 83912, 83909X25, 83898X12, 83894, 83891
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894

References:

1. Ridanpaa M, et al. (2001) Cell 104: 195-203.
2. Bonafe L, et al. (2002) Clin. Genet. 61: 146-151.

Shipping Information

Forms:

>> Gene Sequencing Requisition
>> Prenatal Requisition

Test Codes:

Index: 6125
Known Familial Mutation: 6130
Prenatal (Known Familial Mutation Only): 6131