Microphthalmia/Anophthalmia/Coloboma Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10333 ABCB6 81479,81479 Order Options and Pricing
ADAMTS18 81479,81479
ALDH1A3 81479,81479
ATOH7 81479,81479
BCOR 81479,81479
BMP4 81479,81479
BMP7 81479,81479
C12orf57 81479,81479
CHD7 81407,81479
COL4A1 81408,81479
CRYBA4 81479,81479
FNBP4 81479,81479
FOXE3 81479,81479
GDF3 81479,81479
GDF6 81479,81479
HCCS 81479,81479
HMGB3 81479,81479
IPO13 81479,81479
MAB21L2 81479,81479
MFRP 81479,81479
MITF 81479,81479
NAA10 81479,81479
NDP 81404,81403
NDUFB11 81479,81479
NHS 81479,81479
OTX2 81479,81479
PAX2 81406,81479
PAX6 81479,81479
PITX3 81479,81479
PQBP1 81405,81404
PRR12 81479,81479
PRSS56 81479,81479
PXDN 81479,81479
RAB18 81479,81479
RAB3GAP1 81479,81479
RAB3GAP2 81479,81479
RARB 81479,81479
RAX 81479,81479
RBP4 81479,81479
SHH 81479,81479
SIX6 81479,81479
SMOC1 81479,81479
SOX2 81479,81479
STRA6 81479,81479
TBC1D20 81479,81479
TENM3 81479,81479
TFAP2A 81479,81479
TMEM98 81479,81479
TMX3 81479,81479
VAX1 81479,81479
VSX1 81479,81479
VSX2 81479,81479
YAP1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10333Genes x (53)81479 81403, 81404, 81405, 81406, 81407, 81408, 81479 $1090 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Anophthalmia (A; absence of a globe in the orbit), microphthalmia (M; reduced size of the globe) and coloboma (Greek koloboma, meaning ‘‘mutilated’’ or ‘‘curtailed’’) are an interrelated spectrum of congenital, severe, and rare developmental defects of the globe. Microphthalmia, anophthalmia, and coloboma (MAC) account for a significant portion of childhood visual impairment and blindness worldwide (Gregory-Evans et al. 2004. PubMed ID: 15591273; Skalicky et al. 2013. PubMed ID: 24177921). Of note, 3.2-11.2% children with blindness are reported to be presenting with M (Harding and Moosajee. 2019. PubMed ID: 31416264; Verma and Fitzpatrick. 2007. PubMed ID: 18039390). Estimated birth prevalence ranges from 0.6-4.2/100 000 births for A; 2-17/100,000 births for M; and 2-14/100,000 births for coloboma (Skalicky et al. 2013. PubMed ID: 24177921). The overall MAC prevalence is estimated to be two in 10,000 live births (Morrison et al. 2002. PubMed ID: 11826019).

MAC may be unilateral or bilateral. Over 50% of A/M affected individuals have systemic abnormalities such as hypothalamic–pituitary disorder, mild dysmorphic facial features and short stature, urogenital anomalies, cryptorchidism and/or micropenis in males, developmental delay, seizures, oesophageal atresia or tracheoesophageal fistula and hearing loss (Ragge et al. 2005. PubMed ID: 15812812), but only 25% of these are part of distinct and well-defined syndromes (Bakrania et al. 2007. PubMed ID: 17522144). Unilateral A/M cases often have developmental anomalies of the other eye; including coloboma, lens, and optic nerve (Ragge et al. 2007. PubMed ID: 17914432). Coloboma is frequently seen in association with other developmental defects, including craniofacial anomalies, skeletal defects, and genitourinary anomalies (Gregory-Evans et al. 2004. PubMed ID: 15591273).

Genetic diagnosis and counselling in managing these conditions is often challenging due to the genetic heterogeneity, incomplete penetrance and possible mosaicism. The risk of recurrence of A/M in the siblings without a clear etiology or family history is 10–15% (Verma and Fitzpatrick. 2007. PubMed ID: 18039390). Early diagnosis and multidisciplinary input impact the overall development of the child and the emotional well-being of the family. Of note, the Microphthalmia, Anophthalmia and Coloboma Support organization offers specialist advice and family support to children born without eyes or with underdeveloped eyes and their families (Ragge et al. 2007. PubMed ID: 17914432).

Genetics

MAC is genetically heterogeneous. MAC is inherited as an autosomal dominant, autosomal recessive or X-linked trait. MAC has a complex etiology with a wide range of causes, including chromosomal abnormalities, as well as environmental factors (Pedace et al. 2009. PubMed ID: 19254784). Chromosomal duplications, deletions and translocations account for 23–30% of A/M cases (Pedace et al. 2009. PubMed ID: 19254784). Bakrania et al. reported whole SOX2 gene deletions in ~10% of their A/M patient cohort (Bakrania. 2007. PubMed ID: 17522144), which emphasizes the necessity of careful chromosomal analysis (particularly the 3q region that contains the SOX2 gene) (Guichet et al. 2004. PubMed ID: 15503273). 

SOX2 has been identified as a major causative gene in which heterozygous, loss of function variants account for 15–20% of the A/M cases (Reis et al. 2010. PubMed ID: 20140963; Faivre et al. 2006. PubMed ID: 16470798; Ragge et al. 2005. PubMed ID: 15812812; Williamson and FitzPatrick. 2014. PubMed ID: 24859618). The majority of the causative SOX2 sequence variations occur de novo (Williamson et al. 2020. PubMed ID: 20301477). Occasional cases result from parental gonosomal mosaicism (Faivre et al. 2006. PubMed ID: 16470798; Schneider et al. 2008. PubMed ID: 18831064). Approximately 80% of the severe bilateral MAC cases are due to de novo heterozygous loss-of-function pathogenic variants in in SOX2 or OTX2 (Williamson and FitzPatrick. 2014. PubMed ID: 24859618; Wyatt et al. 2008. PubMed ID: 18781617). The cause of the majority of isolated coloboma cases are unknown (Williamson and FitzPatrick. 2014. PubMed ID: 24859618).

Bi-allelic loss-of-function variants in STRA6 (Gerth-Kahlert et al. 2013. PubMed ID: 24498598) are confirmed as an emerging cause of nonsyndromal eye malformations.

Other genes involved in MAC include ADAMTS18,  ALDH1A3,  ATOH7,  BCOR,  BMP4,  BMP7,  CHD7,  CRYBA4,  FOXE3,  GDF3,  GDF6,  HCCS,  HMGB3,  MAB21L2,  MFRP,  MITF,  NAA10,  NDP,  NHS,  OTX2,  PAX2,  PAX6,  PITX3,  PQBP1,  PRSS56,  RARB,  RAX,  RBP4,  SHH,  SIX6,  SMOC1,  SOX2,  STRA6,  TENM3 (alternatively known as ODZ3),  TFAP2A,  TMEM98,  VAX1, VSX2, YAP1,ABCB6, C12orf57, COL4A1, FNBP4, NDUFB11, PRR12, PXDN, RAB1B, RAB3GAP1, RAB3GAP2, TBC1D20, TMX3 and VSX1 (Wimplinger et al. 2006. PubMed ID: 17033964; Tassabehji et al. 1994. PubMed ID: 7874167; Abouzeid et al. 2012. PubMed ID: 22736936; Aldahmesh et al. 2013. PubMed ID: 23167593; Reis et al. 2011. PubMed ID: 21976963; Aldahmesh et al. 2012. PubMed ID: 22766609; Reis et al. 2010. PubMed ID: 20140963; Asai-Coakwell et al. 2009. PubMed ID: 19129173; Billingsley et al. 2006. PubMed ID: 16960806; Okada et al. 2011. PubMed ID: 21194678; Bardakjian et al. 2013 PubMed ID: 20301552; Williamson and FitzPatrick. 2014. PubMed ID: 24859618; Deml et al. 2014. PubMed ID: 24628545; Liegel et al. 2013. PubMed ID: 24239381; Patel. 2019. PubMed ID: 30653986; van Rahden et al. 2015. PubMed ID: 25772934; Leduc et al. 2018. PubMed ID: 29556724; Choi et al. 2015. PubMed ID: 24939590; Matías-Pérez et al. 2018. PubMed ID: 30181649).

Of note, pathogenic variants in FOXE3 have been reported to have autosomal dominant or autosomal recessive inheritance. Dominant variants are those (e.g., c.958T>C (p.*320Argext*72) and c.942dupG (p.Leu315Alafs*117)), which result in extension of the open reading frame beyond the normal stop codon and are reported to have dominant negative effect (Semina et al. 2001. PubMed ID: 11159941; Iseri et al. 2009. PubMed ID: 19708017). Recessive variants (e.g., missense variants) result in altered protein interactions (Iseri et al. 2009. PubMed ID: 19708017).

Normal intrauterine eye development is controlled by a complex network of diffusible signaling molecules such as transcription factors (encoded by SOX2OTX2PAX6, etc.), expression regulators (encoded by YAP1BCORCHD7, etc.), proteins involved in signaling pathways (encoded by BMP4, BMP7, GDF6, etc.) and genes involved in the metabolism of retinoic acid (such as STRA6, ALDH1A3, RARB and RBP4). Disruption of any one of these events has the potential to cause ocular growth and structural defects (Plaisancié et al. 2019. PubMed ID: 30762128; Skalicky et al. 2013. PubMed ID: 24177921).

See individual gene test descriptions for more information on molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

SOX2 has been identified as a major causative gene in which copy number variants and heterozygous, loss of function sequence variants account for 15–20% of MAC cases (Reis et al. 2010. PubMed ID: 20140963; Faivre et al. 2006. PubMed ID: 16470798; Ragge et al. 2005. PubMed ID: 15812812; Williamson and FitzPatrick. 2014. PubMed ID: 24859618). Also, BCOR and OTX2 copy number variants (CNVs) have been reported frequently in patients with MAC spectrum (Human Gene Mutation Database; Hilton et al. 2009. PubMed ID: 19367324). Whole-genome copy number variation analysis in patients with A/M identified CNVs in 17% of the cases (Schilter et al. 2013. PubMed ID: 23701296). Together, sequence analysis, gene-targeted deletion/duplication analysis, and chromosomal copy number variant analysis can identify a genetic cause in 80% of individuals with bilateral A/severe M and in up to 20% of all individuals with MAC spectrum (Bardakjian et al. 2013. PubMed ID: 20301552).

Testing Strategy

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

This panel typically provides 99.8% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with symptoms of Microphthalmia/anophthalmia/coloboma.

Diseases

Name Inheritance OMIM ID
Anterior Segment Mesenchymal Dysgenesis AD 107250
Aphakia, Congenital Primary AD, AR 610256
Branchiooculofacial Syndrome AD 113620
Cataract 11 AR 610623
Cataract 23 AD 610425
Cataract 34, multiple types AD, AR 612968
Cataract, Congenital, X-Linked XL 302200
CHARGE Association AD 214800
Coloboma Of Optic Disc AD 120430
Coloboma, Ocular AD 120200
Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation AD 120433
Congenital Aniridia AD 106210
Corneal Opacification and Other Ocular Anomalies AR 269400
Craniofacial Anomalies And Anterior Segment Dysgenesis Syndrome 614195
Exudative Vitreoretinopathy 2, X-Linked XL 305390
Foveal Hypoplasia And Presenile Cataract Syndrome AD 136520
Glomerulosclerosis, Focal Segmental, 7 AD 616002
Holoprosencephaly 3 AD 142945
Kallmann Syndrome 5 AD 612370
Keratoconus 1 AD 148300
Klippel-Feil Syndrome 3, Autosomal Dominant 613702
Lenz Microphthalmia Syndrome XL 309800
Linear skin defects with multiple congenital anomalies 3 XL 300952
Martsolf Syndrome AR 212720
Microcornea, Myopic Chorioretinal Atrophy, and Telecanthus AR 615458
Microphthalmia Syndromic 3 AD 206900
Microphthalmia Syndromic 5 AD 610125
Microphthalmia Syndromic 6 AD 607932
Microphthalmia Syndromic 7 XL 309801
Microphthalmia Syndromic 9 AR 601186
Microphthalmia With Limb Anomalies AR 206920
Microphthalmia, Isolated 2 610093
Microphthalmia, Isolated 3 AR 611038
Microphthalmia, Isolated 4 AD 613094
Microphthalmia, Isolated 5 AR 611040
Microphthalmia, Isolated 6 AR 613517
Microphthalmia, Isolated 7 AD 613704
Microphthalmia, Isolated 8 AR 615113
Microphthalmia, Isolated, with Coloboma 10 AD 616428
Microphthalmia, Isolated, With Coloboma 3 610092
Microphthalmia, Isolated, With Coloboma 5 AD 611638
Microphthalmia, Isolated, With Coloboma 6 AD 613703
Microphthalmia, isolated, with coloboma 7 AD 614497
Microphthalmia, Isolated, with Coloboma 9 AR 615145
Microphthalmia, syndromic 11 AR 614402
Microphthalmia, syndromic 12 AR 615524
Microphthalmia, Syndromic 13 XL 300915
Microphthalmia/Coloboma and Skeletal Dysplasia Syndrome AR 615877
Mitochondrial complex I deficiency, nuclear type 30 XL 301021
Nance-Horan Syndrome XL 302350
Nanophthalmos 2 AR 609549
Nanophthalmos 4 AD 615972
Norrie Disease XL 310600
Oculofaciocardiodental Syndrome XL 300166
Ogden Syndrome XL 300855
Optic Disc Anomalies with Retinal and/or Macular Dystrophy AR 212550
Optic Nerve Hypoplasia, Bilateral AD 165550
Papillorenal Syndrome AD 120330
Persistent Hyperplastic Primary Vitreous, Autosomal Recessive AR 221900
Peters Anomaly AD 604229
Porencephaly 1 AD 175780
Renpenning Syndrome 1 XL 309500
Retinal arteries, tortuosity of AD 180000
Retinal Dystrophy, Iris Coloboma, and Comedogenic Acne Syndrome AR 615147
Single Upper Central Incisor AD 147250
Temtamy Syndrome AR 218340
Waardenburg Syndrome, Type 2A AD 193510
Warburg Micro Syndrome 1 AR 600118
Warburg Micro Syndrome 2 AR 614225
Warburg Micro Syndrome 3 AR 614222
Warburg Micro Syndrome 4 AR 615663

Related Test

Name
PGxome®

Citations

  • Abouzeid et al. 2012. PubMed ID: 22736936
  • Aldahmesh et al. 2012. PubMed ID: 22766609
  • Aldahmesh et al. 2013. PubMed ID: 23167593
  • Asai-Coakwell et al. 2009. PubMed ID: 19129173
  • Bakrania et al. 2007. PubMed ID: 17522144
  • Bardakjian et al. 2013. PubMed ID: 20301552
  • Billingsley et al. 2006. PubMed ID: 16960806
  • Choi et al. 2015. PubMed ID: 24939590
  • Deml et al. 2014. PubMed ID: 24628545
  • Faivre et al. 2006. PubMed ID: 16470798
  • Gregory-Evans et al. 2004. PubMed ID: 15591273
  • Guichet et al. 2004. PubMed ID: 15503273
  • Harding and Moosajee. 2019. PubMed ID: 31416264
  • Hilton et al. 2009. PubMed ID: 19367324
  • Human Gene Mutation Database (Biobase).
  • Iseri et al. 2009. PubMed ID: 19708017
  • Leduc et al. 2018. PubMed ID: 29556724
  • Liegel et al. 2013. PubMed ID: 24239381
  • Matías-Pérez et al. 2018. PubMed ID: 30181649
  • Morrison et al. 2002. PubMed ID: 11826019
  • Okada et al. 2011. PubMed ID: 21194678
  • Patel. 2019. PubMed ID: 30653986
  • Pedace et al. 2009. PubMed ID: 19254784
  • Plaisancié et al. 2019. PubMed ID: 30762128
  • Ragge et al. 2005. PubMed ID: 15812812
  • Ragge et al. 2007. PubMed ID: 17914432
  • Reis et al. 2010. PubMed ID: 20140963
  • Reis et al. 2011. PubMed ID: 21976963
  • Schilter et al. 2013. PubMed ID: 23701296
  • Semina et al. 2001. PubMed ID: 11159941
  • Skalicky et al. 2013. PubMed ID: 24177921
  • Tassabehji et al. 1994. PubMed ID: 7874167
  • van Rahden et al. 2015. PubMed ID: 25772934
  • Verma and Fitzpatrick. 2007. PubMed ID: 18039390
  • Williamson and FitzPatrick. 2014. PubMed ID: 24859618
  • Williamson et al. 2020. PubMed ID: 20301477
  • Wimplinger et al. 2006. PubMed ID: 17033964
  • Wyatt et al. 2008. PubMed ID: 18781617

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.

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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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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