RLBP1-Related Disorders via the RLBP1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8695 RLBP1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8695RLBP181479 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing 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

Retinitis pigmentosa (RP; OMIM # 268000) or rod cone dystrophies (RCDs) represent a group of hereditary retinal dystrophies with a worldwide prevalence of ~1 in 4000 (Booij et al. J Med Genet 42 (11): e67, 2005). RP is clinically characterized by retinal pigment deposits visible on fundus examination, nyctalopia (night blindness), followed by progressive loss of peripheral vision in daylight, which eventually leads to blindness (van Soest et al. Surv Ophthalmol 43(4):321-334,1999).

A unique atypical variant of RP denoted Bothnia dystrophy (BD; OMIM # 607475) has been identified in the northern Swedish population with an estimated prevalence of ~1 in 2500 due to founder effect (Köhn et al. Invest Ophthalmol Vis Sci 49(7):3172-3177, 2008). BD is characterized by early, severe nyctalopia in early childhood, fundus changes similar to retinitis punctata albescens (RPA), and progressive macular and peripheral retinal degeneration with progressive reduction of visual acuity (VA) and visual fields (VF) that leads to legal blindness in early adulthood (Burstedt et al. Arch Ophthalmol 119(2):260-267, 2001; Burstedt et al. Golovleva Arch Ophthalmol 128(8):989-995, 2010).

RPA (OMIM #136880) is an autosomal recessive (ar) form of RP characterized by nyctalopia, discrete uniform white flecks in the fundus, reduced VA and VF, progressive attenuation of retinal arterioles, abnormal fundus pigmentation and abnormal electroretinogram (ERG) amplitudes (Fishman et al. Arch Ophthalmol 122(1):70-75, 2004).

Fundus albipunctatus (FA; OMIM #136880) is an infrequent form of apparently stationary nyctalopia. FA is characterized by the presence of numerous white flecks in the fundus with a greater concentration in the mid and peripheral regions of the retina, which is comparable to RPA (Naz et al. Br J Ophthalmol 95(7):1019-1024, 2011).

Newfoundland rod–cone dystrophy (NFRCD; OMIM # 607476) ophthalmoscopic appearance is similar to that of RPA with a different age of onset. NFRCD is typically evident in the first decade of life with rapid progression, leading to legal blindness by the second to fourth decades (Eichers et al. Am J Hum Genet 70(4):955-964. 2002).

Genetics

Mutations in the RLBP1 gene (OMIM # 607475), which is located on 15q26, are associated with various types of autosomal recessive retinal dystrophies such as RPA (Morimura et al. Invest Ophthalmol Vis Sci 40(5):1000-1004, 1999; Demirci et al. Am J Ophthalmol 138(1):171-173.2004; Fishman et al., 2004; Nakamura et al. Am J Ophthalmol 139(6):1133-1135.2005), arRP (Maw et al. Nat Genet 17(2):198-200, 1997), BD (Burstedt et al. Invest Ophthalmol Vis Sci 40(5):995-1000, 1999 and Burstedt et al., 2001), NFRCD (Eichers et al., 2002) and FA (Naz et al., 2011). RLBP1 encodes the cellular retinaldehyde-binding protein (CRALBP), which is mainly expressed in the retinal pigment epithelium (RPE) and Müller cells of the retina. CRALBP plays a crucial role in retinoid metabolism and visual pigment regeneration in the retina, where it functions as a carrier of endogenous retinoids such as 11-cis-retinol and 11-cis-retinal. Photoisomerization of 11-cis-retinal to all-trans-retinal in the retinal photoreceptor cells triggers phototransduction and ultimately results in visual sensation (Köhn et al., 2008; Stecher et al. Biochemistry 38(41):13542-13550, 1999). There are ~ 20 mutations have been reported in RLBP1, which includes missense, splicing, small deletions and gross deletions (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

All BD (20/20) affected patients from seven Vasterbotten families in northern Sweden were homozygous for the c.700C>T (p.Arg234Trp) mutation in exon 7 of the RLBP1 gene, which explains the founder effect (Burstedt et al. Invest Ophthalmol Vis Sci 40(5):995-1000, 1999). Köhn et al. (2008) also tested 121 individuals affected with arRP in the same population for the c.700C>T mutation and found that 67 were homozygous and 10 were heterozygous for that mutation (Köhn et al. Invest Ophthalmol Vis Sci 49(7):3172-3177, 2008).

Testing Strategy

This test provides full coverage of all coding exons of the RLBP1 gene 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 full 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

All patients with symptoms suggestive of Retinitis pigmentosa (RP), Bothnia dystrophy (BD), Retinitis Punctata Albescens (RPA), Fundus albipunctatus (FA) and Newfoundland rod–cone dystrophy (NFRCD) are candidates for this test. Family members of patients who have known mutations and carrier testing for at-risk family members are also candidates.

Gene

Official Gene Symbol OMIM ID
RLBP1 180090
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
RHO-Related Disorders via the RHO Gene
Cone-Rod Dystrophy Panel
Flecked Retina Disorder Panel
Fundus Albipunctatus With or Without Cone Dystrophy via the RDH5 Gene
Retinitis Pigmentosa (includes RPGR ORF15) Panel
Retinitis Pigmentosa via the PRPH2 (RDS) Gene

Citations

  • Booij JC. 2005. Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. Journal of Medical Genetics 42: e67–e67. PubMed ID: 16272259
  • Burstedt, M.S. and Golovleva, I. (2010). "Central retinal findings in Bothnia dystrophy caused by RLBP1 sequence variation." Arch Ophthalmol 128(8):989-995. PubMed ID: 20696998
  • Burstedt, M.S. et al. (1999). "Bothnia dystrophy caused by mutations in the cellular retinaldehyde-binding protein gene (RLBP1) on chromosome 15q26." Invest Ophthalmol Vis Sci 40(5):995-1000. PubMed ID: 10102298
  • Burstedt, M.S. et al. (2001). "Ocular phenotype of bothnia dystrophy, an autosomal recessive retinitis pigmentosa associated with an R234W mutation in the RLBP1 gene." Arch Ophthalmol 119(2):260-267. PubMed ID: 11176989
  • Demirci, F.Y. et al. (2004). "A novel compound heterozygous mutation in the cellular retinaldehyde-binding protein gene (RLBP1) in a patient with retinitis punctata albescens." Am J Ophthalmol 138(1):171-173. PubMed ID: 15234312
  • Eichers, E. R. et al. (2002). "Newfoundland rod-cone dystrophy, an early-onset retinal dystrophy, is caused by splice-junction mutations in RLBP1." Am J Hum Genet 70(4):955-964. PubMed ID: 11868161
  • Fishman, G.A. et al. (2004). "Novel mutations in the cellular retinaldehyde-binding protein gene (RLBP1) associated with retinitis punctata albescens: evidence of interfamilial genetic heterogeneity and fundus changes in heterozygotes." Arch Ophthalmol 122(1):70-75. PubMed ID: 14718298
  • Human Gene Mutation Database (Bio-base).
  • Humbert, G. et al. (2006). "Homozygous deletion related to Alu repeats in RLBP1 causes retinitis punctata albescens." Invest Ophthalmol Vis Sci 47(11):4719-4724. PubMed ID: 17065479
  • Köhn, L. et al. (2008). "Carrier of R14W in carbonic anhydrase IV presents Bothnia dystrophy phenotype caused by two allelic mutations in RLBP1." Invest Ophthalmol Vis Sci 49(7):3172-3177. PubMed ID: 18344446
  • Maw, M.A. et al. (1997). "Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa." Nat Genet 17(2):198-200. PubMed ID: 9326942
  • Morimura, H. et al. (1999). "Recessive mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein in a form of retinitis punctata albescens." Invest Ophthalmol Vis Sci 40(5):1000-1004. PubMed ID: 10102299
  • Nakamura, M. et al. (2005). "Novel mutation in RLBP1 gene in a Japanese patient with retinitis punctata albescens." Am J Ophthalmol 139(6):1133-1135. PubMed ID: 15953459
  • Naz, S. et al. (2011). "Mutations in RLBP1 associated with fundus albipunctatus in consanguineous Pakistani families." Br J Ophthalmol 95(7):1019-1024. PubMed ID: 21447491
  • Stecher, H. et al. (1999). "Isomerization of all-trans-9- and 13-desmethylretinol by retinal pigment epithelial cells." Biochemistry 38(41):13542-13550. PubMed ID: 10521261
  • Van Soest S., Westerveld A. 1999. Survey of ophthalmology. 43: 321-34. PubMed ID: 10025514

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

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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


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