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 Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 8099 | ALDH18A1 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks 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.
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.
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
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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ORDER OPTIONS
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