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Pelger-Huet Anomaly and Greenberg Skeletal Dysplasia via the LBR Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8255 LBR 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8255LBR81479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

Pelger-Huet Anomaly (PHA) was first reported in the late 1920s and early 1930s and is characterized by hyposegmentation of nuclei and abnormal chromatin organization in blood granulocytes (Pelger, K Ned T Geneesk 72:1178, 1928; Huet, G.H. Maandschr. Kindergeneesk 1:173, 1932). Data suggest PHA is a due to a deficiency of the lamin B receptor protein within the nuclear membrane (Hoffman et al. 2002). The abnormal neutrophils found in PHA patients are reported to function properly (Johnson et al. 1980), but severe (homozygous) forms of the disease may be accompanied by mental retardation and skeletal anomalies including disproportionate body stature, macrocephaly, ventricular septal defect, and short fingers (Hoffman et al. 2002). A related disorder, Hydrops-ectopic calcification-"moth-eaten" (HEM) or Greenberg skeletal dysplasia is characterized by a phenotype similar to that found in severe forms of PHA and may also present with fetal hydrops and abnormal chondro-osseous calcification often resulting in prenatal death (Waterham et al. 2003; Clayton et al. 2010). Since healthy relatives of patients with Greenberg skeletal dysplasia were found to have abnormal granulocyte neuclei, it is suspected that classic PHA and Greenberg skeletal dysplasia represent the heterozygous and homozygous states of lamin B receptor deficiency, respectively (Waterham et al. 2003).

Genetics

Mutations in the LBR gene are involved with autosomal dominant Pelger-Huet Anomaly (PHA) (Hoffman et al. 2002) and autosomal recessive Greenberg skeletal dysplasia (Waterham et al. 2003). The LBR gene encodes the lamin B receptor which comprises an N-terminal lamin B / DNA-binding domain and a C-terminal sterol reductase-like domain (Holmer et al. 1998). The lamin B receptor is highly conserved evolutionarily and helps maintain the structural integrity of the inner-nuclear membrane through binding to chromatin and nuclear lamins (Burke and Ellenberg 2002). Decreased sterol reductase function of the lamin B receptor is found in Greenberg skeletal dystrophy patients (Waterham et al. 2003) thereby identifying Greenberg skeletal dysplasia as a disorder of cholesterol biosynthesis. The frequency of PHA is around 0.01-0.1% worldwide, but is higher in areas of northern Sweden and southeastern Germany (Hoffman et al. 2002); the frequency of Greenberg skeletal dysplasia is unclear. Causative variants are spread throughout the 13 coding exons of the LBR gene and include roughly equal proportions of missense / nonsense mutations and small deletions or insertions.

Clinical Sensitivity - Sequencing with CNV PGxome

The incidence of PHA is around 0.01-0.1% worldwide, but is higher in areas of northern Sweden and southeastern Germany (Hoffman et al. 2002); the frequency of Greenberg skeletal dysplasia is unclear. Only a small number of PHA and Greenberg skeletal dysplasia cases have been reported in the literature so the rate of mutation detection among patients remains unclear.

To date, no large genomic deletions or duplications in the LBR gene have been reported in PHA or Greenberg skeletal dysplasia patients.

Testing Strategy

This test provides full coverage of all coding exons of the LBR gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

All patients with clinical and biochemical features of PHA or Greenberg skeletal dysplasia and relatives of these patients. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LBR.

Gene

Official Gene Symbol OMIM ID
LBR 600024
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Greenberg Dysplasia AR 215140
Pelger-Huet Anomaly AD 169400

Citations

  • Burke B, Ellenberg J. 2002. Remodelling the walls of the nucleus. Nat. Rev. Mol. Cell Biol. 3: 487–497. PubMed ID: 12094215
  • Clayton P, Fischer B, Mann A, Mansour S, Rossier E, Veen M, Lang C, Baasanjav S, Kieslich M, Brossuleit K. 2010. Mutations causing Greenberg dysplasia but not Pelger anomaly uncouple enzymatic from structural functions of a nuclear membrane protein. Nucleus 1: 354. PubMed ID: 21327084
  • Hoffmann K, Dreger CK, Olins AL, Olins DE, Shultz LD, Lucke B, Karl H, Kaps R, Müller D, Vayá A, Aznar J, Ware RE, et al. 2002. Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger–Huët anomaly). Nature Genetics 31:410-414. PubMed ID: 12118250
  • Holmer L, Pezhman A, Worman HJ. 1998. The human lamin B receptor/sterol reductase multigene family. Genomics 54: 469–476. PubMed ID: 9878250
  • Johnson CA, Bass DA, Trillo AA, Snyder MS, DeChatelet LR. 1980. Functional and metabolic studies of polymorphonuclear leukocytes in the congenital Pelger-Huet anomaly. Blood 55: 466–469. PubMed ID: 6244014
  • Waterham HR, Koster J, Mooyer P, Noort G van, Kelley RI, Wilcox WR, Wanders RJA, Hennekam RCM, Oosterwijk JC. 2003. Autosomal Recessive HEM/Greenberg Skeletal Dysplasia Is Caused by 3 beta-hydroxysterol delta 14-reductase Deficiency Due to Mutations in the Lamin B Receptor Gene. Am J Hum Genet 72: 1013–1017. PubMed ID: 12618959

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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.
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