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 which includes 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 + CNV which includes 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 genes included in Albinism panel

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
AP3B1 603401 Hermansky-Pudlak syndrome type 2 AR 18
BLOC1S3 609762 Hermansky-Pudlak syndrome 8 AR 2
BLOC1S6 604310 Hermansky-pudlak syndrome 9 AR 0
DTNBP1 607145 Hermansky-Pudlak syndrome 7 AR 6
EDN3 131242 congenital central hypoventilation syndrome; Waardenburg syndrome type 4B; Hirschsprung disease 4 AD, AR 8
EDNRB 131244 Waardenburg syndrome type 4A; Hirschsprung disease, susceptibility to, 2; ABCD syndrome AD, AR 5
GPR143 300808 Albinism, Ocular, Type I; Nystagmus 6, congenital, X-linked XL 7
HPS1 604982 Hermansky-Pudlak syndrome type 1 AR 13
HPS3 606118 Hermansky-Pudlak syndrome type 3 AR 10
HPS4 606682 Hermansky-Pudlak syndrome type 4 AR 6
HPS5 607521 Hermansky-Pudlak syndrome type 5 AR 8
HPS6 607522 Hermansky-Pudlak syndrome type 6 AR 3
KIT 164920 Mast cell disease; Piebaldism; Spermatocytic seminoma, somatic; acute myeloid leukemia; gastrointestinal stromal tumor AD 14
LRMDA 614537 Albinism, oculocutaneous, type VII AR 3
LYST 606897 Chediak-Higashi syndrome AR 31
MC1R 155555 oculocutaneous albinism type 2; skin/hair/eye pigmentation 2 AR 6
MITF 156845 Albinism, Ocular, With Sensorineural Deafness; Tietz Syndrome; Waardenburg syndrome type 2A; Melanoma, Cutaneous Malignant, Susceptibility To, 8 AD, AR 9
MLPH 606526 Griscelli syndrome, type 3 AR 2
MYO5A 160777 Griscelli syndrome, type 1 AR 31
OCA2 611409 oculocutaneous albinism type 2 AR 25
PAX3 606597 Waardenburg syndrome, type 3; Waardenburg syndrome type 1 AD, AR 10
RAB27A 603868 Griscelli syndrome, type 2 AR 6
SLC24A5 609802 Oculocutaneous albinism-6 AR 0
SLC45A2 606202 Oculocutaneous albinism, type IV AR 8
SNAI2 602150 Piebaldism; Waardenburg syndrome type 2d AD, AR 1
SOX10 602229 PCWH syndrome; Waardenburg syndrome type 2E AD 17
TYR 606933 Albinism, Ocular, With Sensorineural Deafness; oculocutaneous albinism type 1A; Skin/hair/eye pigmentation 3; Albinism, oculocutaneous, type IB AD, AR 15
TYRP1 115501 Albinism, oculocutaneous, type III AR 8