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GeneDx
Test Information Sheet
207 Perry Parkway
Gaithersburg, MD 20877
Phone: 301-519-2100
Fax: 301-519-2892
E-mail: [email protected]
www.genedx.com
RMRP Gene Analysis in Cartilage-Hair Hypoplasia, Metaphyseal
Dysplasia without Hypotrichosis, and Anauxetic Dysplasia
Also known as: Metaphyseal chondrodysplasia, McKusick type; Spondylometaepiphyseal dysplasia Menger
Type (Anauxetic Dysplasia)
Mendelian Inheritance in Man Number: 250250 (Cartilage Hair Hypoplasia); 250460 (Metaphyseal
Dysplasia without Hypotrichosis); 607095 (Anauxetic Dysplasia)
Clinical features:
Cartilage-hair hypoplasia (CHH) is a pleiotropic disorder characterized by short-limbed dwarfism, coneshaped epiphyses, metaphyseal flaring and irregularities, sparse and light colored hair of abnormally
small caliber, immunological defects manifested by unusual susceptibility to chickenpox, and other
hematological anomalies such as neutropenia and anemia. Some patients may also have Hirschsprung
disease, impaired spermatogenesis, and increased susceptibility to cancer. Skeletal abnormalities may
include incomplete extension at the elbows, chest deformities, lumbar lordosis, joint laxity, bowed legs,
genu varum, and excessively long fibula distally relative to the tibia, in addition to dwarfism. Hypoplasia
of the cartilage is seen microscopically. Metaphyseal dysplasia without hypotrichosis was initially
described as a distinct entity from CHH with identical skeletal features, and lacking hypotrichosis and
immunodeficiency. Anauxetic dysplasia is a form of extreme short stature of prenatal onset, hypodontia,
and mild mental retardation. Recent data shows that these three disorders are allelic as each condition is
caused by mutations in the RNase MRP (RMRP) gene. The RMRP gene encodes the RNA subunit of a
RNA processing enzyme complex (endoribonuclease).
Inheritance pattern: Autosomal recessive
Reasons for referral:
1. Confirmation of a clinical diagnosis
2. Differentiation between CHH and other causes of dwarfism
3. Identification of patients at increased risk of infections or cancer
4. Genetic counseling
5. Prenatal diagnosis
Test method:
The RMRP gene consists of a promoter region and an RNA coding region of 267 nucleotides. Using
genomic DNA obtained from the submitted biological material the entire sequence will be screened by
bi-directional sequencing. Mutations found in the first person of a family to be tested are confirmed by
repeat analysis using sequencing, restriction fragment analysis, or another appropriate method.
Test sensitivity:
In previous studies, an RMRP mutation was identified in 94% of the patients who fit the clinical
description for CHH. The sensitivity for patients with metaphyseal dysplasia without hypotrichosis and
anauxetic dysplasia is unknown.
Information Sheet on CHH, Metaphyseal Dysplasia and Anauxetic Dysplasia Page 1 of 2 © GeneDx Rev. Date: 3/13
Mutation spectrum:
The most common mutation in the RMRP gene is a GA point mutation at nucleotide 70. This
accounts for 92% of Finnish mutations and 48% of patients from other ethnic backgrounds. One study
found 36 different mutations in 135 families with CHH (Ridanpaa et al., 2002). The mutations were
scattered throughout most of the gene, although the region between nucleotides 23 and 62 were spared in
their population. The types of mutations seen in the RMRP gene include those affecting the promoter
region, small changes in conserved nucleotides, and insertions and duplications at 5’ end of the
transcript. The analysis of the RMRP gene in 120 controls revealed an unusually high density of singlenucleotide polymorphisms in and around the gene; the significance of this finding is not clear.
Specimen Requirements and Shipping/Handling:
• Blood: A single tube with 1-5 mL whole blood in EDTA. Ship overnight at ambient temperature,
using a cool pack in hot weather. Specimens may be refrigerated for up to 7 days prior to shipping.
• Buccal Brushes: As an alternative to blood, use a GeneDx buccal kit (others not accepted). Submit
by mail. Buccal brushes are not accepted on children less than 6 months of age.
• Prenatal Diagnosis: For prenatal testing for a known mutation in the RMRP gene, please refer to the
specimen requirements table on our website at: http://www.genedx.com/test-catalog/prenatal/. Ship
specimen overnight at ambient temperature, using a cool pack in hot weather.
Required Forms:
• Sample Submission (Requisition) Form – complete all pages
• Payment Options Form or Institutional Billing Instructions
For test codes, prices, CPT codes, and turn-around-times, please refer to the “Cartilage-Hair Hypoplasia,
Metaphyseal Dysplasia without Hypotrichosis, and Anauxetic Dysplasia” page on our website:
www.genedx.com
References Cited:
Ridanpaa M, et al., Mutations in the RNA Component of RNase MRP Cause a Pleiotropic Human Disease,
Cartilage-Hair Hypoplasia Cell 104:195-203 (2001); Bonafe L, et al., RMRP gene sequence analysis confirms
a cartilage-hair hypoplasia variant with only skeletal manifestations and reveals a high density of singlenucleotide polymorphisms Clin Genet 61:146-151 (2002); Ridanpaa, M, et al., Worldwide mutation spectrum
in cartilage-hair hypoplasia: ancient founder origin of the major 70AG mutation of the untranslated RMRP
Eur J of Hum Genet 10:439-447 (2002).
Information Sheet on CHH, Metaphyseal Dysplasia and Anauxetic Dysplasia Page 2 of 2 © GeneDx Rev. Date: 3/13