1. NGS panel - Genetic testing for albinism

Albinism

June 13, 2018

Disease summary

Albinism is an inherited genetic condition which is characterized by reduced or nomelanin pigment 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

1 in 17,000 -20,000 1-3

Major clinical symptoms 1, 2:

  • Hypopigmentation of iris and iris translucency
  • Hypopigmentation of skin
  • Hypopigmented hair
  • Vision problems (reduced sharpness, nystagmus and photophobia)
  • Increased risk of melanoma on long-term sun exposure

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 tests:

  • Albinism NGS Panel Plus which includes full gene sequencing of the genes AP3B1, BLOC1S3, BLOC1S6, C10ORF11, DTNBP1, EDN3, EDNRB, GPR143, HPS1, HPS3, HPS4, HPS5, HPS6, KIT, LYST, MC1R, MITF, MLPH, MYO5A, OCA2, PAX3, RAB27A, SLC24A5, SLC45A2, SNAI2, SOX10, TYR, TYRP1
  • Albinism NGS Panel Plus + CNV which includes full gene sequencing and additionally detection of large deletions and duplications from the NGS data
  • 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.


Table 1. Overview of the genes in CENTOGENE´s Albinism panel:

Gene OMIM Protein Associated diseases (OMIM)
AP3B1 603401 Adaptor-related protein complex 3 Hermansky-Pudlak syndrome 2 (608233)
BLOC1S3 609762 Biogenesis of lysosome-related organelles complex 1, subunit 3 Hermansky-Pudlak syndrome 8 (614077)
BLOC1S6 604310 Biogenesis of lysosome-related organelles complex 1, subunit 6 Hermansky-Pudlak syndrome 9 (614171)
DYNBP1 607145 Dysbindin Hermansky-Pudlak syndrome 7 (614076)
C10ORF11 614537 Chromosome 10 open reading frame 11 Albinism, oculocutaneous, type VII (615179)
EDN3 131242 Endothelin 3 Central hypoventilation syndrome, congenital (209880); Waardenburg syndrome, type 4B (613265); Hirschsprung disease, susceptibility to, 4 (613712)
EDNRB 131244 Endothelin receptor B ABCD syndrome (600501), Waardenburg syndrome, type 4A (277580); Hirschsprung disease, susceptibility to, 2 (600155)
GPR143 300808 G protein-coupled receptor 143 Nystagmus 6, congenital, X-linked (300814); Ocular albinism, type I, Nettleship-Falls type (300500)
HPS1 604982 HPS1 Hermansky-Pudlak syndrome 1 (203300)
HPS3 606118 HPS3 Hermansky-Pudlak syndrome 3 (614072)
HPS4 606682 HPS4 Hermansky-Pudlak syndrome 4 (614073)
HPS5 607521 HPS5 Hermansky-Pudlak syndrome 5 (614074)
HPS6 607522 HPS6 Hermansky-Pudlak syndrome 6 (614075)
KIT 164920 KIT oncogene Gastrointestinal stromal tumor, familial (606764); Germ cell tumors, somatic (273300); Leukemia, acute myeloid (601626); Mast cell disease (154800); Piebaldism (172800)
LYST 606897 Lysosomal trafficking regulator Chediak-Higashi syndrome (214500)
MC1R 155555 Melanocortin 1 receptor Skin/hair/eye pigmentation 2, blond hair/fair skin (266300); Analgesia from kappa-opioid receptor agonist, female-specific (613098); Albinism, oculocutaneous, type II, modifier of (203200); Melanoma, cutaneous malignant, 5 (613099)
MITF 1156845 Microphthalmia-associated transcription factor COMMAD syndrome (617306); Tietz albinism-deafness syndrome (103500); Waardenburg syndrome, type 2A (193510); Waardenburg syndrome/ocular albinism, digenic (103470); Melanoma, cutaneous malignant, susceptibility to, 8 (614456)
MLPH 606526 Melanophilin Griscelli syndrome, type 3 (609227)
MYO5A 160777 Myosin VA Griscelli syndrome, type 1 (214450)
OCA2 611409 OCA2 Albinism, oculocutaneous, type II (203200); Skin/hair/eye pigmentation 1, blond/brown hair (227220)
PAX3 606597 Paired box gene 3 Craniofacial-deafness-hand syndrome (122880); Rhabdomyosarcoma 2, alveolar (268220); Waardenburg syndrome, type 1 (193500); Waardenburg syndrome, type 3 (148820)
RAB27A 603868 RAS-associated protein 27A Griscelli syndrome, type 2 (607624)
SLC24A5 609802 Solute carrier family protein 24 (sodium/potassium/calcium exchanger) Albinism, oculocutaneous, type VI (113750); Skin/hair/eye pigmentation 4, fair/dark skin (113750)
SLC45A2 606202 Solute carrier family 45; membrane-associated transporter protein Albinism, oculocutaneous, type IV (606574); Skin/hair/eye pigmentation 5, black/nonblack hair (227240)
SNAI2 602150 Neural crest transcription factor slug Piebaldism (172800), Waardenburg syndrome, type 2D (608890)
SOX10 602229 SRY-box 10 PCWH syndrome (609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (611584); Waardenburg syndrome, type 4C (613266)
TYR 606933 Tyrosinase Albinism, oculocutaneous, type IA (203100); Albinism, oculocutaneous, type IB (606952); Waardenburg syndrome/albinism, digenic (103470); Skin/hair/eye pigmentation 3, blue/green eyes (601800) 
TYRP1 115501 Tyrosinase-related protein 1 Albinism, oculocutaneous, type III (203290); Skin/hair/eye pigmentation, variation in, 11 (612271)