1. NGS panel - Genetic testing for albinism

Albinism

March 09, 2017

Disease summary

Albinism is an inherited genetic condition that reduces the amount of melanin pigment formed in the eyes, skin, and/or hair. The most common form of albinism is oculocutaneous albinism (OCA), caused by a reduction of melanin biosynthesis in the melanocytes resulting in hypopigmentation of the hair, skin, and eyes1.

Autosomal recessive

Incidence 1/20,000 1-3

Major clinical symptoms 1, 2:

  • Hypopigmentation of iris and iris translucency
  • Hypopigmentation of skin
  • Various degrees of congenital nystagmus
  • Reduced pigmentation of the retinal pigment epithelium
  • Foveal hypoplasia
  • Reduced visual acuity
  • A degree of color vision impairment

Less common clinical symptoms:

  • White hair
  • Very pale skin
  • Light-colored irises

Presence of the following clinical features 1, 2:

  • Hypopigmentation of the skin and hair
  • Infantile nystagmus
  • Markedly reduced iris pigment with iris transillumination
  • Reduced retinal pigmentation
  • Foveal hypoplasia
  • Reduction in visual acuity
  • Strabismus
  • Reduced stereoscopic vision
  • Altered visually evoked potentials (VEP)

Identification of a heterozygous pathogenic variant in one of the following genes (Table 1) 3, 4:

  • TYR (frequency of pathogenic variants approximately 44%) 5
  • OCA2 (17%) 6
  • TYRP1 (1%) 7
  • SLC45A2 (7%) 7
  • GPR143 (5%) 7
  • SLC24A5 (0,5%) 7

There is no cure for albinism to date, but treatment for albinism can relieve symptoms 3-7.

  • Protective sunglasses and clothing
  • Sunscreen to protect the skin from UV rays
  • Surgery on the muscles of the eyes to correct abnormal eye movements 1,2.
  • Hermansky-Pudlak syndrome
  • Chediak-Higashi syndrome
  • Griscelli syndrome
  • Waardenburg syndrome type II
  • Ichthyosis

To confirm/establish the diagnosis, CENTOGENE offers the following testing strategy for Albinism using NGS Panel Genomic:

Step 1: Whole genome sequencing from a single filter card (drop of blood), covering the entire genic region (coding region, exon/intron boundaries, intronic and promoter) for all the genes included in the Albinism panel. Copy Number Variants analysis derived from NGS data is also included.

Step 2: If no pathogenic variant is identified in Step1, continue with bioinformatics analysis covering genes that are either implicated or associated with overlapping phenotype or similar pathways.   

  • Individuals with a positive family history of albinism
  • Individuals with most common symptoms of albinism (regardless of family history)

Confirmation of a clinical diagnosis through genetic testing of albinism can allow for genetic counseling and may direct medical management.


Overview of the genes in CENTOGENE´s Albinism panel:

Gene OMIM Protein Function
AP3B1 603401 Adaptor-related protein complex 3 Organelle biogenesis associated with melanosomes
BLOC1S3 609762 Biogenesis of lysosome-related organelles complex 1, subunit 3 Required for normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules
BLOC1S6 604310 Biogenesis of lysosome-related organelles complex 1, subunit 6 Required for normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules
DYNBP1 607145 Dysbindin A key component of biogenesis of lysosome-related organelles complex-1, which regulates the trafficking of proteins in the lysosomal pathway
C10ORF11 614537 Chromosome 10 open reading frame 11 A gene that is important for melanocyte differentiation and function
EDN3 131242 Endothelin 3 Plays an important role in neural crest cells, including menalocytes
EDNRB 131244 Endothelin receptor B Endothelin receptor type B together plays an important role in neural crest cells, including melanocytes
GPR143 300808 G protein-coupled receptor 143 G protein-coupled receptor exclusively expressed by melanocytes and retinal pigment epithelium
HPS1 604982 HPS1 HPS genes encodes proteins called melanosomes that produce and distribute melanin
HPS3 606118 HPS3 HPS genes encodes proteins called melanosomes that produce and distribute melanin
HPS4 606682 HPS4 HPS genes encodes proteins called melanosomes that produce and distribute melanin
HPS5 607521 HPS5 HPS genes encodes proteins called melanosomes that produce and distribute melanin
HPS6 607522 HPS6 HPS genes encodes proteins called melanosomes that produce and distribute melanin
KIT 164920 KIT oncogene Regulates development of melanocytes and other cell types
LYST 606897 Lysosomal trafficking regulator Provides instructions for making a protein known as the lysosomal trafficking regulator
MC1R 155555 Melanocortin 1 receptor Provides instructions for making a protein called the melanocortin 1 receptor, that plays an important role in normal pigmentation
MITF 1156845 Microphthalmia-associated transcription factor MITF plays a role in the development of various cell types, including neural crest-derived melanocytes and optic cup-derived retinal pigment epithelial cells
MLPH 606526 Melanophilin Provides instructions for making a protein called melanophilin, found in melanocytes
MYO5A 160777 Myosin VA Melanophilin interacts with proteins produced from the MYO5A and RAB27A genes to form a complex that transports melanosomes to the outer edges of melanocytes
OCA2 611409 OCA2 This protein is located in melanocytes, where it plays a role in normal vision.
PAX3 606597 Paired box gene 3 Plays a critical role in the formation of tissues and organs during embryonic development, including development of melanocytes
RAB27A 603868 RAS-associated protein 27A Melanophilin interacts with proteins produced from the MYO5A and RAB27A genes to form a complex that transports melanosomes to the outer edges of melanocytes
SLC24A5 609802 Solute carrier family protein 24 (sodium/potassium/calcium exchanger) The human SLC24A5 gene has a role in skin pigmentation
SLC45A2 606202 Solute carrier family 45; membrane-associated transporter protein Encodes a melanocyte differentiation antigen that is expressed in a high percentage of melanoma cell lines
SNAI2 602150 Neural crest transcription factor slug Plays a role in the formation of tissues during embryonic development, including pigment-producing cells called melanocytes
SOX10 602229 SRY-box 10 SOX10 protein is essential for the formation of nerves in the intestine and melanocytes
TYR 606933 Tyrosinase Tyrosinase catalyzes the conversion of tyrosine to melanin
TYRP1 115501 Tyrosinase-related protein 1 The TYRP1 gene provides instructions for making an enzyme called tyrosinase-related protein 1

More information on CENTOGENE´s Albinism panel can be found in our genetic test catalogue.