Alstrom Syndrome via the ALMS1 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
265 ALMS1$1850.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
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.

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 ALMS1$690.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

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

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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).
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).
Testing Strategy
This test involves bidirectional Sanger sequencing using genomic DNA of all 23 coding exons (exon 1-23) of the ALMS1 gene, plus ~20 bp of flanking non-coding DNA for each exon. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.
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).


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


Name Inheritance OMIM ID
Alstrom Syndrome 203800


Genetic Counselors
  • 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
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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