Oculocutaneous Albinism, Ocular Albinism, Hermansky-Pudlak Syndrome, Chediak-Higashi Syndrome
NGS panel

Genes
(full
coding region):		 AP3B1, AP3D1, BLOC1S3, BLOC1S5, BLOC1S6, CACNA1F, DTNBP1, GPR143, HPS1, HPS3, HPS4, HPS5, HPS6, LRMDA, LYST, MC1R, OCA2, RAB27A, SLC24A5, SLC45A2, TYR, TYRP1

List of diseases covered by the panel
Lab method: NGS panel with CNV analysis
TAT: 6-9 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Deletion/duplication analysis

Genes: GPR143, OCA2, TYR
Lab method: MLPA
TAT: 4-6 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of different forms/subtypes of Oculocutaneous albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Oculocutaneous albinism (OCA) is a group of rare inherited disorders characterized by a reduction or complete lack of melanin pigment in the skin, hair and eyes. These conditions are caused by mutations in specific genes that are relevant to the production of melanin pigment in melanocytes. Patients usually have vision problems such as reduced sharpness, nystagmus and photophobia. There are seven types of OCA (OCA1-7) caused by mutations in seven different genes.

Ocular albinism (OA) primarily affects the eyes, and does not significantly affect the color of the skin and hair. The most common form of OA is type 1 (OA1), also named X-linked ocular albinism. OA1 is characterized by vision abnormalities in affected males. Vision deficits are present at birth and do not become more severe over time. Other forms of OA are much rarer and may be associated with additional signs and symptoms such as hearing loss.

Hermansky-Pudlak syndrome (HPS) is a multisystem, hereditary disorder characterized mainly by albinism with visual impairment and blood platelet dysfunction with prolonged bleeding. The symptoms of HPS are present at birth. It is the third most prevalent form of albinism. There are 11 types of HPS (1-11), which can be distinguished by their signs and symptoms and underlying genetic cause.

Chediak-Higashi syndrome (CHS) is an inherited, complex, immune disorder that usually occurs in childhood (at birth or shortly thereafter) characterized by oculocutaneous albinism, nervous system abnormalities, immune deficiency with an increased susceptibility to infections, and a tendency to easy bruising and abnormal bleeding.

The test covers known genetic causes of all aforementioned syndromes.

Oculocutaneous albinism, Hermansky-Pudlak syndrome, and Chediak-Higashi syndrome are inherited in an autosomal recessive inheritance pattern. Ocular albinism type 1 is inherited in an X-linked pattern.

Oculocutaneous albinism occurring in all populations, with an estimate prevalence of 1:20 000 people worldwide. Ocular albinism type 1 affects at least 1: 60 000 males. Hermansky-Pudlak syndrome is estimated to affect 1:500 000 to 1 000 000 individuals worldwide. Type 1 is more common in the northwestern part of Puerto Rico where about 1: 1800 people are affected. Type 3 is common in people from central Puerto Rico. Chediak-Higashi syndrome is a very rare disorder. About 200 cases of the condition have been reported worldwide. 85% of affected individuals progress the accelerated phase.

References:
Hayashi M, Suzuki T. Oculocutaneous Albinism Type 4. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; November 17, 2005. PMID:20301683
Huizing M, Malicdan MCV, Gochuico BR, et al. Hermansky-Pudlak Syndrome. 2000 Jul 24 [Updated 2017 Oct 26]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. PMID: 20301464
Huizing M, Malicdan MCV, Wang JA, et al. Hermansky-Pudlak syndrome: Mutation update. Hum Mutat. 2020;41(3):543-580. doi:10.1002/humu.23968. PMID:31898847
Lewis RA. Oculocutaneous Albinism Type 1. 2000 Jan 19 [Updated 2013 May 16]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. PMID:20301345
Lewis RA. Oculocutaneous Albinism Type 2. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; July 17, 2003. PMID: 20301410
Lewis RA. Ocular Albinism, X-Linked. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; March 12, 2004. PMID:20301517
Merideth MA, Introne WJ, Wang JA, O’Brien KJ, Huizing M, Gochuico BR. Genetic variants associated with Hermansky-Pudlak syndrome. Platelets. 2020;31(4):544-547. doi:10.1080/09537104.2019.1663810. PMID:32436471
Pennamen P, Le L, Tingaud-Sequeira A, et al. BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome [published online ahead of print, 2020 Jun 22]. Genet Med. 2020;10.1038/s41436-020-0867-5. doi:10.1038/s41436-020-0867-5. PMID:32565547
Toro C, Nicoli ER, Malicdan MC, Adams DR, Introne WJ. Chediak-Higashi Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; March 3, 2009. PMID:20301751