Alstrom Syndrome via the ALMS1 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
15143 ALMS1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15143ALMS181479 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

  • Anthony Krentz, PhD

Clinical Features and Genetics

Clinical Features

Alström syndrome (AS) is a pleiotropic disorder characterized by retinal degeneration (occurs within the first year of life), childhood obesity, sensorineuronal hearing loss, Insulin resistance, type 2 diabetes, dilated cardiomyopathy and urological, renal, hepatic and pulmonary dysfunctions. Estimated prevalence is less than 1:100,000 (Alstrom et al. 1959; Collin et al. 2002; Marshall et al. 2007). Although AS bears many similarities to Bardet-Biedl syndrome (BBS), there is no cognitive impairment, polydactyly, or hypogonadism in AS. Also, the onset of visual problems differs from BBS (average age of onset is 8.5 years) (Alstrom et al. 1959; Marshall et al. 2012; Marshall et al. 2007). The retinal degeneration, nystagmus and reduced visual acuity usually present in AS overlap with the clinical findings in Achromatopsia and Leber congenital amaurosis (Marshall et al. 2012; Marshall et al. 2007; Russell-Eggitt et al. 1989).

Genetics

Alström syndrome is inherited as an autosomal recessive disorder (Alstrom et al. 1959; Goldstein and Fialkow 1973), and is caused by mutations in the ALMS1 gene (Collin et al. 2002). ALMS1 encodes the Alström syndrome protein 1, which is localized to centrosomes and the base of cilia. Although, the precise function of the ALMS1 protein is unknown, its cellular localization suggests a role in microtubule organization, intracellular transport, and the assembly and function of basal bodies and cilia. Basic pathophysiology probably involve impairment of intracellular trafficking and ciliary dysfunction, which explains symptoms overlap with other ciliopathies such as BBS (Collin et al. 2002; Collin 2005; Hearn et al. 2005). Exon 1 comprises a polyglutamate tract; so far, no association has been found between the length of the tract and AS occurrence (Marshall et al. 2007). All types of mutations (missense, nonsense, frameshift, splicing and gross deletions) have been documented in ALMS1 (Collin et al. 2002; Hearn et al. 2002; Marshall et al. 2007; Aldahmesh et al. 2009; Bond et al. 2005). Mutations in exon 16 have correlated with a more severe disease phenotype (Joy et al. 2007).

Clinical Sensitivity - Sequencing with CNV PG-Select

Mutation screening in a population of 250 AS affected individuals from 206 apparently unrelated kindreds identified ALMS1 causative mutations (79 mutations) in 92 kindreds (~37%) (Marshall et al. 2007). The majority of the mutations (55/79) occurred in exons 10 or 16.

Although rare, gross deletions and a duplication have been reported in ALMS1 (Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Generation sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the ALMS1 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 symptoms consistent with Alström syndrome. Infants with dilated cardiomyopathy should also be considered for ALMS1 gene sequencing (Bond et al. 2005). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ALMS1.

Gene

Official Gene Symbol OMIM ID
ALMS1 606844
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Alstrom Syndrome AR 203800

Citations

  • Aldahmesh MA, Abu-Safieh L, Khan AO, Al-Hassnan ZN, Shaheen R, Rajab M, Monies D, Meyer BF, Alkuraya FS. 2009. Allelic heterogeneity in inbred populations: the Saudi experience with Alström syndrome as an illustrative example. Am. J. Med. Genet. A 149A: 662–665. PubMed ID: 19283855
  • Alstrom CH, Hallgren B, Nilsson LB, Asander H. 1959. Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness: a specific syndrome (not hitherto described) distinct from the Laurence-Moon-Bardet-Biedl syndrome: a clinical, endocrinological and genetic examination based on a large pedigree. Acta Psychiatr Neurol Scand Suppl 129: 1–35.
    PubMed ID: 13649370
  • Bond J, Flintoff K, Higgins J, Scott S, Bennet C, Parsons J, Mannon J, Jafri H, Rashid Y, Barrow M, Trembath R, Woodruff G, Rossa E, Lynch S, Sheilds J, Newbury-Ecob R, Falconer A, Holland P, Cockburn D, Karbani G, Malik S, Ahmed M, Roberts E, Taylor G, Woods CG. 2005. The importance of seeking ALMS1 mutations in infants with dilated cardiomyopathy. Journal of Medical Genetics 42: e10. PubMed ID: 15689433
  • Collin GB, Marshall JD, Ikeda A, So WV, Russell-Eggitt I, Maffei P, Beck S, Boerkoel CF, Sicolo N, Martin M, Nishina PM, Naggert JK. 2002. Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome. Nature Genetics 31: 74-8. PubMed ID: 11941369
  • Collin GB. 2005. Alms1-disrupted mice recapitulate human Alstrom syndrome. Human Molecular Genetics 14: 2323–2333. PubMed ID: 16000322
  • Goldstein JL, Fialkow PJ. 1973. The Alström syndrome. Report of three cases with further delineation of the clinical, pathophysiological, and genetic aspects of the disorder. Medicine (Baltimore) 52: 53–71. PubMed ID: 4689172
  • Hearn T, Renforth GL, Spalluto C, Hanley NA, Piper K, Brickwood S, White C, Connolly V, Taylor JFN, Russell-Eggitt I, Bonneau D, Walker M, et al. 2002. Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome. Nature Genetics 31: 79-83. PubMed ID: 11941370
  • Hearn T, Spalluto C, Phillips VJ, Renforth GL, Copin N, Hanley NA, Wilson DI. 2005. Subcellular localization of ALMS1 supports involvement of centrosome and basal body dysfunction in the pathogenesis of obesity, insulin resistance, and type 2 diabetes. Diabetes 54: 1581–1587. PubMed ID: 15855349
  • Human Gene Mutation Database (Bio-base).
  • Joy T, Cao H, Black G, Malik R, Charlton-Menys V, Hegele RA, Durrington PN. 2007. Alstrom syndrome (OMIM 203800): a case report and literature review. Orphanet Journal of Rare Diseases 2: 49. PubMed ID: 18154657
  • Marshall JD, Hinman EG, Collin GB, Beck S, Cerqueira R, Maffei P, Milan G, Zhang W, Wilson DI, Hearn T, Tavares P, Vettor R, Veronese C, Martin M, So WV, Nishina PM, Naggert JK. 2007. Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. Human Mutation 28: 1114–1123. PubMed ID: 17594715
  • Marshall JD, Paisey RB, Carey C, Macdermott S. 2012. Alström Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301444
  • Russell-Eggitt IM, Taylor DS, Clayton PT, Garner A, Kriss A, Taylor JF. 1989. Leber’s congenital amaurosis–a new syndrome with a cardiomyopathy. British journal of ophthalmology 73: 250–254. PubMed ID: 2713302

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

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1) Select Test Method (Backbone)


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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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