Cartilage-hair Hypoplasia (CHH) and Related Disorders via the RMRP Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7805 RMRP 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7805RMRP81479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Cartilage-hair hypoplasia (OMIM#250250, aka McKusick-type metaphyseal chondrodysplasia) is a pleiotropic disease, characterized by disproportionate short stature, hypoplastic hair, and metaphseal abnormalities. Other common features include defective immunity manifested by unusual susceptibility to chickenpox, risk for malignancies, Hirschsprung disease, hypoplastic anemia, and impaired spermatogenesis (Ridanpaa et al. Eur J Hum Genet 10:439-447, 2002). Metaphyseal dysplasia without hypotrichosis (MDWH; OMIM#250460), manifesting only as short stature and metaphyseal dysplasia, is thought to be a variant of CHH (Bonafe et al. Clin Genet 61:146-151, 2002). Anauxetic dysplasia (AD; OMIM#607095) is the severe form in the spectrum, characterized by extreme disproportionate short stature, hypodontia, and mild mental retardation (Thiel et al. Am J Hum Genet 81:519-529, 2007).

Genetics

Cartilate-hair hypoplasia (CHH) and its related disorders (MDWH and AD) are inherited in an autosomal recessive manner. All three disorders are caused by variants in RMRP gene. RMRP encodes the RNA component of the mitochondrial RNA-processing endonuclease (MRP), which is a ubiquitously expressed eukaryotic endoribonuclease that cleaves various RNAs, including ribosomal, messenger, and mitochondrial RNAs (Ridanpaa et al. Am J Med Genet 121C:81-83, 2003). The gene product is an untranslated RNA, which is essential for RNase activity. Variants found in RMRP can be classified into two categories: insertions, duplications, or triplications in the promoter between TATA box and the transcription initiation site and variants in the transcribed region. The promoter variants can result in inefficient transcription initiation, while the ones in the transcribed region usually disrupt base-pairing required for conserved secondary structure and interaction with protein subunits. No clear genotype-phenotype correlation has been established. CHH is especially frequent among the Amish and Finnish populations; the carrier frequencies are 1:19 and 1:76, respectively. The most prevalent CHH-associated RMRP variant is g.70A>G, which is found in >90% Amish and Finnish patients and 48% of non-Finnish patients (Ridanpaa et al. Eur J Hum Genet 10:439-447, 2002).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test is predicted to detect disease variants in >90% patients with CHH (Hermanns et al. Am J Med Genet 140A:2121-2130, 2006; Ridanpaa et al. Eur J Hum Genet 10:439-447, 2002). The sensitivity for patients with MDWH or AD is unknown.

Testing Strategy

This test provides full coverage of the transcribed region of the RMRP gene, plus ~100 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with clinical and radiological features consistent with disorders in MDWH-CHH-AD spectrum and family members of patients who have known RMRP variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RMRP.

Gene

Official Gene Symbol OMIM ID
RMRP 157660
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Bonafe, L., et.al. (2002). "RMRP gene sequence analysis confirms a cartilage-hair hypoplasia variant with only skeletal manifestations and reveals a high density of single-nucleotide polymorphisms." Clin Genet 61(2): 146-51. PubMed ID: 11940090
  • Hermanns, P., et.al. (2006). "RMRP mutations in cartilage-hair hypoplasia." Am J Med Genet A 140(19): 2121-30. PubMed ID: 16838329
  • Ridanpaa, M., et.al. (2002). "Worldwide mutation spectrum in cartilage-hair hypoplasia: ancient founder origin of the major70A-->G mutation of the untranslated RMRP." Eur J Hum Genet 10(7): 439-47. PubMed ID: 12107819
  • Ridanpaa, M., et.al. (2003). "The major mutation in the RMRP gene causing CHH among the Amish is the same as that found in most Finnish cases." Am J Med Genet C Semin Med Genet 121C(1): 81-3. PubMed ID: 12888988
  • Thiel, C. T., et.al. (2007). "Type and level of RMRP functional impairment predicts phenotype in the cartilage hair hypoplasia-anauxetic dysplasia spectrum." Am J Hum Genet 81(3): 519-29. PubMed ID: 17701897

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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