Autosomal Recessive Cutis Laxa Type IIA (ARCL2A) and Wrinkly Skin Syndrome (WSS) via the ATP6V0A2 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
8031 ATP6V0A2 81479 81479,81479 $640 Order Options

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.

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

Targeted Testing

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

Turnaround Time

18 days on average

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Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Autosomal recessive cutis laxa type IIA (ARCL2A, also referred as Derby type; OMIM 219200) is characterized by hypotonia, over-folded skin, dysmorphic facial features at birth, development delay, and mental retardation. Other common manifestations include enlarged anterior fontanelle, congenital hip dislocation, high myopia, strabismus, and seizures caused by malformation of cortical and cerebella tissues. The dysmorphic features and abnormal neurological symptoms become severe over time, and some patients may lose the ability to walk by adolescence. However, the skin conditions may improve over time. A few patients have abnormalities in the cardiovascular, urogenital, and hematological systems. Wrinkly skin syndrome (WSS; OMIM 278250) is a relatively mild disorder. Patients with the syndrome may have reduced skin elasticity, dental abnormalities (small teeth, delayed eruption, caries), and delayed closure of the fontanel (Hucthagowder et al. Hum Mol Genet 18:2149–2165, 2009; Morava et al. Eur J Hum Genet 17:1099-1110, 2009; Maldergem et al. Genereview, 2011).

Genetics

ARCL2A and WSS are inherited in an autosomal recessive manner and are caused by variants in ATP6V0A2, which encodes the a2 subunit of the vesicular H+ pump and is a member of the ATPase protein complex family. Variants in ATP6V0A2 impair Golgi vesicle trafficking and prevent the production of functional glycosylation. This results in reduced or abnormal elastic fiber formation. Most known ATP6V0A2 variants are truncating variants, which were found throughout the gene. Missense variants involving proline residues near or within the transmembrane domain are shown to cause ARCL2A (p.P87L, p.P405L, and p.P792R). In addition, a large in-frame deletion (c.1936_2055del, p.E646_685del) was reported in four unrelated patients originating from Iran and Turkey (Hucthagowder et al. Hum Mol Genet 18(12):2149–2165 2009; Morava et al. Eur J Hum Genet 17:1099-1110, 2009; Maldergem et al. GeneReviews, 2011).

Testing Strategy

This test provides full coverage of all coding exons of the ATP6V0A2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing with CNV PG-Select

Two studies reported that the ATP6V0A2 variants were identified in 27 out of the 29 clinically-diagnosed ARCL2A or WSS families/patients screened by transferrin isoelectric focusing (Kornak et al. 2008; Hucthagowder et al. 2009).

Indications for Test

Individuals with clinical diagnosed ARCLA2 and WSS. Individuals diagnosed by transferrin isoelectric focusing, mass spectrometry, or skin biopsy are preferred. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ATP6V0A2.

Gene

Official Gene Symbol OMIM ID
ATP6V0A2 611716
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Autosomal Recessive Cutis Laxa Type 3A (ARCL3A) via the ALDH18A1 Gene
Congenital Disorders of Glycosylation (CDG) Panel
Cutis Laxa via the PYCR1 Gene
Cutis Laxa, Type 1B (ARCL1B) via the EFEMP2 Gene
Geroderma Osteodysplasticum (GO) via the GORAB Gene
Macrocephaly, Alopecia, Cutis Laxa and Scoliosis (MACS) Syndrome via the RIN2 Gene
Menkes Disease and Hereditary Motor Neuropathy via the ATP7A Gene

Citations

  • Hucthagowder et al. Loss-of-function mutations in ATP6V0A2 impair vesicular trafficking, tropoelastin secretion and cell survival. Hum Mol Genet  18(12):2149-2165, 2009. PubMed ID: 19321599
  • Kornak et al. Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2. Nat Genet. 40:32-34, 2008 PubMed ID: 18157129
  • Maldergem et al. GeneReviews, 2011 PubMed ID: 20301755
  • Morava et al. Autosomal recessive cutis laxa syndrome revisited. Eur J Hum Genet  17:1099-1110, 2009. PubMed ID: 19401719

Ordering/Specimens

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Specimen Types

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