Autosomal Recessive Cutis Laxa Type 3A (ARCL3A) via the ALDH18A1 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
8099 ALDH18A1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8099ALDH18A181479 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

Clinical Features and Genetics

Clinical Features

Cutis laxa autosomal recessive type IIIA (ARCL3A, OMIM#219150) is characterized by dysmorphic facial features, sparse hair, ophthalmologic defects, intrauterine growth retardation, and cutis laxa. Patients with ALDH18A1 variants show symptoms of developmental delay (prenatal and postnatal), thin/wrinkled skin, joint hypermobility, low birth weight, short status, and congenital microcephaly. Other less common features include inguinal hernia, cataract, corneal clouding, neonatal seizures, hypotonia, and progressive neurodegeneration. A few cases were reported with inborn error of proline/ornithine metabolism. Notably, in some patients, wrinkled skin disappears by adolescence and joint hypermobility improves over time (Baumgartner et al. Hum Molec Genet 9:2853-2858, 2000; Bicknell et al. Eur J Hum Genet 16:1176-1186, 2008; Skidmore et al. Am J Med Genet 155A:1848-1856, 2011).

Genetics

ALDH18A1 (OMIM# 138250) encodes the enzyme delta-1-pyrroline-5-carboxylate synthetase (P5CS), which is involved in the first two steps of proline biosynthesis. Variants in the ALDH18A1 gene cause ARCL3A, an autosomal recessive disorder with highly variable clinical presentations. To date, only two missense (c.251G>A, p.R84Q; c.2350C>T, p.H784Y) and one splicing (c.1923+1G>A, p. Val601Glyfs*24) variant were identified in three unrelated consanguineous families. The variant p.R84Q was shown to disrupt the highly conserved arginine residue in the P5CS glutamyl kinase domain, which leads to impaired proline and urea cycle metabolism. In contrast, the variant p.H784Y was speculated to affect the role of the proline in neurotransmission (Baumgartner et al. 2000; Bicknell et al. 2008; Skidmore et al. 2011 and Mohamed et al. J Inherit Metab Dis, 34:907-916, 2011).

Clinical Sensitivity - Sequencing with CNV PG-Select

To date, ALDH18A1 variants were only reported in three families (Baumgartner et al. Hum Molec Genet 9:2853-2858, 2000; Bicknell et al. Eur J Hum Genet 16:1176-1186, 2008; and Skidmore et al. Am J Med Genet 155A:1848-1856, 2011), so the sensitivity of the test is currently unknown.

Testing Strategy

This test provides full coverage of all coding exons of the ALDH18A1 gene, plus ~10 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 features consistent with ARCLIIIA and the family members of patients who have known ALDH18A1 variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ALDH18A1.

Gene

Official Gene Symbol OMIM ID
ALDH18A1 138250
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Autosomal Recessive Cutis Laxa Type 3A AR 219150

Related Tests

Name
Autosomal Recessive Cutis Laxa Type IIA (ARCL2A) and Wrinkly Skin Syndrome (WSS) via the ATP6V0A2 Gene
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

  • Baumgartner et al. (2000). Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. Hum Molec Genet 9(19): 2853-2858. PubMed ID: 11092761
  • Baumgartner et al. Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. Hum Mol Genet 9(19):2853-2858, 2000.
  • Bicknell et al. (2008). A missense mutation in ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome. Eur J Hum Genet 16(10): 1176-1186. PubMed ID: 18478038
  • Mohamed et al. Metabolic cutis laxa syndromes. J Inherit Metab Dis 34(4): 907-916, 2011. PubMed ID: 21431621
  • Skidmore et al. Further expansion of the phenotypic spectrum associated with mutations in ALDH18A1, encoding Δ¹-pyrroline-5-carboxylate synthase (P5CS). Am J Med Genet A 155A(8): 1848-1856, 2011. PubMed ID: 21739576

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.
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