Posterior Microphthalmia via the PRSS56 Gene
- Summary and Pricing
- Clinical Features and Genetics
|Test Code||Test Copy Genes||Individual Gene Price||CPT Code Copy CPT Codes|
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The great majority of tests are completed within 18 days.
PRSS56, which encodes a trypsin-like serine protease, is classified as a member of the chymotrypsin family as the encoded protein carries a highly conserved triad consisting of Asp191-His145-Ser286 (similar to trypsin triad Asp102-His57-Ser195), which is required for the catalytic activity of the protein (Gal et al. 2011).
MCOP was found to be highly prevalent in the Faroe Islands due to a founder effect (carrier frequency 3.2%). Patients of the Faroese families were either homozygous for c.926G>C (p.Trp309Ser) or compound heterozygous for c.926G>C and c.526C>G (p.Arg176Gly) variants in PRSS56. Molecular modeling of the p.Trp309Ser variant showed substantially reduced enzyme affinity and reactivity toward in vivo protein substrates. A homozygous single nucleotide deletion c.1066dupC was identified in five arMCOP patients from a consanguineous Tunisian family, which is predicted to result in translational frameshift and protein truncation (p.Gln356Argfs*148). In the Saudi population, PRSS56 pathogenic variants were shown to be the major cause of arMCOP (Orr et al. 2011; Gal et al. 2011; Said et al. 2013; Nowilaty et al. 2013). So far, over 20 pathogenic variants (missense variants and single nucleotide duplications) have been reported in the PRSS56 gene, which the majority are missense variants (90%) (Human Gene Mutation Database; Orr et al. 2011; Gal et al. 2011).
Indications for Test
|Official Gene Symbol||OMIM ID|
- Genetic Counselor Team - email@example.com
- Madhulatha Pantrangi, PhD - firstname.lastname@example.org
- Gal A, Rau I, El Matri L, Kreienkamp H-J, Fehr S, Baklouti K, Chouchane I, Li Y, Rehbein M, Fuchs J, Fledelius HC, Vilhelmsen K, Schorderet DF, Munier FL, Ostergaard E, Thompson DA, Rosenberg T. 2011. Autosomal-Recessive Posterior Microphthalmos Is Caused by Mutations in PRSS56, a Gene Encoding a Trypsin-Like Serine Protease. The American Journal of Human Genetics 88: 382–390. PubMed ID: 21397065
- Hmani-Aifa M, Salem S Ben, Benzina Z, Bouassida W, Messaoud R, Turki K, Khairallah M, Rebaï A, Fakhfekh F, Söderkvist P, Ayadi H. 2009. A genome-wide linkage scan in Tunisian families identifies a novel locus for non-syndromic posterior microphthalmia to chromosome 2q37.1. Hum. Genet. 126: 575–587. PubMed ID: 19526372
- Human Gene Mutation Database (Bio-base).
- Nowilaty SR, Khan AO, Aldahmesh MA, Tabbara KF, Al-Amri A, Alkuraya FS. 2013. Biometric and molecular characterization of clinically diagnosed posterior microphthalmos. Am. J. Ophthalmol. 155: 361–372.e7. PubMed ID: 23127749
- Orr A, Dubé M-P, Zenteno JC, Jiang H, Asselin G, Evans SC, Caqueret A, Lakosha H, Letourneau L, Marcadier J, Matsuoka M, Macgillivray C, Nightingale M, Papillon-Cavanagh S, Perry S, Provost S, Ludman M, Guernsey DL, Samuels ME. 2011. Mutations in a novel serine protease PRSS56 in families with nanophthalmos. Molecular vision 17: 1850. PubMed ID: 21850159
- Said MB, Chouchène E, Salem SB, Daoud K, Largueche L, Bouassida W, Benzina Z, Ayadi H, Söderkvist P, Matri L, Hmani-Aifa M. 2013. Posterior microphthalmia and nanophthalmia in Tunisia caused by a founder c.1059_1066insC mutation of the PRSS56 gene. Gene 528: 288–294. PubMed ID: 23820083
Bi-Directional Sanger Sequencing
Nomenclature for sequence variants was from the Human Genome Variation Society (http://www.hgvs.org). 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.
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).
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.
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- 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.