X-linked Lenz Microphthalmia Syndrome and Lethal Ogden Syndrome via the NAA10 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
8617 NAA10 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8617NAA1081479 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Lenz microphthalmia syndrome (LMS) is a X-linked disorder characterized by unilateral or bilateral microphthalmia accompanied by multiple congenital extraocular abnormalities. Extraocular symptoms include developmental delay, skeletal abnormalities, genitourinary malformations, cleft lip and palate, digital anomalies, and anomalies of the ears and teeth. Mild to severe intellectual disability and seizures are seen in about 60% of affected males (Traboulsi et al. 1988; Esmailpour et al. 2014).

Ogden syndrome (OS) is an X-linked lethal disorder in infancy with severe developmental delays and a unique combination other symptoms including facial dysmorphic features, skin, skeletal, cardiac, genital and neurological abnormalities (Rope et al. 2011; Myklebust et al. 2015). X-chromosome inactivation was analyzed in heterozygous, affected OS women and all four women showed skewed X-inactivation (Myklebust et al. 2015).

Besides lethality, a distinct difference between MLS and OS is microphthalmia or anophthalmia, which only present in MLS. Reduced expressivity of the symptoms have been reported in female carriers (Rope et al. 2011; Esmailpour et al. 2014).

Genetics

Hemizygous variants in NAA10 have been reported to be causative for allelic disorders LMS and OS. The mutation spectrum cannot be precisely described due to the limited number of documented cases. So far, only a missense (p.Ser37Pro) and a splice-site variant (c.471+2T>A) have been reported to be causative (Rope et al. 2011; Esmailpour et al. 2014). The splice-site variant in NAA10 has been shown to affect the retinoic acid signaling pathway that is is important for normal eye development and resulted in LMS. Whereas the missense variant was shown to reduce N-terminal acetyltransferase activity and resulted in severe phenotype OS (Rope et al. 2011; Esmailpour et al. 2014).

NAA10-encoded N-terminal acetyltransferase (NAT) is a ubiquitously expressed protein, which is involved in protein N-terminal acetylation (NTA). Recently, NAT has been shown to be involved in post-translational NTA, lysine acetylation, and NAT/KAT-independent functions (Dörfel and Lyon 2015). NTA is a commonly occurring protein modification in eukaryotes that has an important role in the modulation of protein-protein interaction, protein degradation, complex formation, subcellular targeting, and protein folding (Aksnes et al. 2015; Dörfel and Lyon 2015). NAT was also shown to be involved in the retinoic acid signaling pathway and normal eye development (Esmailpour et al. 2014).

LMS is genetically heterogeneous; NAA10 (MCOPS1 locus) and BCOR (MCOPS2 locus) are the only two genes so far identified (Ng 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be precisely estimated for Lenz microphthalmia and Ogden syndrome patients as they are rare disorders with a limited number of documented cases. Analytical sensitivity should be high because all NAA10 pathogenic variants reported are detectable by sequencing. No gross deletions or duplications have been reported so far (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the NAA10 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

All patients with symptoms suggestive of MLS and OS are candidates.

Gene

Official Gene Symbol OMIM ID
NAA10 300013
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Lenz Microphthalmia Syndrome XL 309800
Ogden Syndrome XL 300855

Citations

  • Aksnes H, Hole K, Arnesen T. 2015. Molecular, cellular, and physiological significance of N-terminal acetylation. Int Rev Cell Mol Biol 316: 267–305. PubMed ID: 25805127
  • Dörfel MJ, Lyon GJ. 2015. The biological functions of Naa10 - From amino-terminal acetylation to human disease. Gene 567: 103–131. PubMed ID: 25987439
  • Esmailpour T, Riazifar H, Liu L, Donkervoort S, Huang VH, Madaan S, Shoucri BM, Busch A, Wu J, Towbin A, Chadwick RB, Sequeira A, Vawter MP, Sun G, Johnston JJ, Biesecker LG, Kawaguchi R, Sun H, Kimonis V, Huang T. 2014. A splice donor mutation in NAA10 results in the dysregulation of the retinoic acid signalling pathway and causes Lenz microphthalmia syndrome. Journal of Medical Genetics 51: 185–196. PubMed ID: 24431331
  • Human Gene Mutation Database (Bio-base).
  • Myklebust LM, Damme P Van, Stove SI, Dorfel MJ, Abboud A, Kalvik TV, Grauffel C, Jonckheere V, Wu Y, Swensen J, Kaasa H, Liszczak G, Marmorstein R, Reuter N, Lyon GJ, Gevaert K, Arnesen T. 2015. Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects. Human Molecular Genetics 24: 1956–1976. PubMed ID: 25489052
  • NG D. 2014. Lenz Microphthalmia Syndrome. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle. PubMed ID: 20301694
  • Rope AF, Wang K, Evjenth R, Xing J, Johnston JJ, Swensen JJ, Johnson WE, Moore B, Huff CD, Bird LM, Carey JC, Opitz JM, Stevens CA, Jiang T, Schank C, Fain HD, Robison R, Dalley B, Chin S, South ST, Pysher TJ, Jorde LB, Hakonarson H, Lillehaug JR, Biesecker LG, Yandell M, Arnesen T, Lyon GJ. 2011. Using VAAST to Identify an X-Linked Disorder Resulting in Lethality in Male Infants Due to N-Terminal Acetyltransferase Deficiency. The American Journal of Human Genetics 89: 28–43. PubMed ID: 21700266
  • Traboulsi EI, Lenz W, Gonzales-Ramos M, Siegel J, Macrae WG, Maumenee IH. 1988. The Lenz microphthalmia syndrome. Am. J. Ophthalmol. 105: 40–45. PubMed ID: 3276203

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.

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

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

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.

Total Price: $
×
Copy Text to Clipboard
×