List of diseases covered by Oculocutaneous Albinism, Ocular Albinism, Hermansky-Pudlak Syndrome, Chediak-Higashi Syndrome NGS panel

List of diseases covered by
Oculocutaneous Albinism, Ocular Albinism, Hermansky-Pudlak Syndrome, Chediak-Higashi Syndrome
NGS panel

Gene Condition
AP3B1 Hermansky-Pudlak syndrome 2
AP3D1 Hermansky-Pudlak syndrome 10
BLOC1S3 Hermansky-Pudlak syndrome 8
BLOC1S5 Hermansky-Pudlak syndrome 11
BLOC1S6 Hermansky-pudlak syndrome 9
DTNBP1 Hermansky-Pudlak syndrome 7
GPR143 Nystagmus 6, congenital, X-linked;
Ocular albinism, type I, Nettleship-Falls type
HPS1 Hermansky-Pudlak syndrome 1
HPS3 Hermansky-Pudlak syndrome 3
HPS4 Hermansky-Pudlak syndrome 4
HPS5 Hermansky-Pudlak syndrome 5
HPS6 Hermansky-Pudlak syndrome 6
LRMDA Albinism, oculocutaneous, type VII
MC1R Albinism, oculocutaneous, type II, modifier of
LYST Chediak-Higashi syndrome
OCA2 Albinism, oculocutaneous, type II
SLC24A5 Albinism, oculocutaneous, type VI
SLC45A2 Albinism, oculocutaneous, type IV
TYR Albinism, oculocutaneous, type IA;
Albinism, oculocutaneous, type IB;
Waardenburg syndrome/albinism, digenic
TYRP1 Albinism, oculocutaneous, type III

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

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

Genes
(full
coding region):
AP3B1, AP3D1, BLOC1S3, BLOC1S5, BLOC1S6, DTNBP1, GPR143, HPS1, HPS3, HPS4, HPS5, HPS6, LRMDA, LYST, MC1R, OCA2, 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. Carrier testing for at-risk family members
  3. Genetic counseling
  4. Prenatal diagnosis for known familial mutation

Albinism is a group of congenital disorders of melanin production characterized by variable hypopigmentation and vision defects, including impaired visual acuity, nystagmus, strabismus, astigmatism, and photophobia. The complete or partial absence of pigment may affect the eyes, skin and hair (oculocutaneous albinism) or only the eyes (ocular albinism).

Additionally, there are also syndromic forms of albinism such as Hermansky-Pudlak syndrome and Chediak-Higashi syndrome.

The prevalence of all known forms of albinism is estimated to be 1:17 000 newborns.

Oculocutaneous albinism (OCA) is divided into seven types, which are caused by mutations in the respective genes: OCA1 (TYR), OCA2 (OCA2), OCA3 (TYRP1), OCA4 (SLC45A2), OCA5 (chromosome 4q24), OCA6 (SLC24A5), and OCA7 (C10orf11). All forms of OCA are inherited autosomal recessively.

Ocular albinism is caused by mutations in the GPR143 gene and is inherited in an X-linked manner.

Mutations in HPS1 (HPS1), AP3B1 (HPS2), HPS3 (HPS3), HPS4 (HPS4), HPS5 (HPS5), HPS6 (HPS6), DTNBP1 (HPS7), BLOC1S3 (HPS8), and BLOC1S6 (HPS9) genes are known to cause different types of Hermansky-Pudlak syndrome (HPS). HPS is inherited in an autosomal recessive manner and characterized by OCA, bleeding disorders, pulmonary fibrosis, and granulomatous colitis.

The LYST gene is know to be associated with Chediak-Higashi syndrome (CHS). CHS is inherited in an autosomal recessive manner and characterized by partial OCA, immunodeficiency, peripheral neuropathy, and bleeding tendency.

List of diseases covered by Hermansky-Pudlak Syndrome NGS panel

List of diseases covered by
Hermansky-Pudlak Syndrome NGS panel

Gene Condition
AP3B1 Hermansky-Pudlak syndrome 2
AP3D1 Hermansky-Pudlak syndrome 10
BLOC1S3 Hermansky-Pudlak syndrome 8
BLOC1S5 Hermansky-Pudlak syndrome 11
BLOC1S6 Hermansky-pudlak syndrome 9
DTNBP1 Hermansky-Pudlak syndrome 7
HPS1 Hermansky-Pudlak syndrome 1
HPS3 Hermansky-Pudlak syndrome 3
HPS4 Hermansky-Pudlak syndrome 4
HPS5 Hermansky-Pudlak syndrome 5
HPS6 Hermansky-Pudlak syndrome 6

Hermansky-Pudlak Syndrome NGS panel

Hermansky-Pudlak Syndrome NGS panel

Genes
(full coding
region):
AP3B1, AP3D1, BLOC1S3, BLOC1S5, BLOC1S6, DTNBP1, HPS1, HPS3, HPS4, HPS5, HPS6

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

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of Hermansky-Pudlak syndrome types
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Hermansky-Pudlak syndrome (HPS) is a group of rare hereditary disorders characterized by defective biogenesis of lysosome-related organelles. Clinical manifestations include oculocutaneous albinism, bleeding diathesis, and in some individuals pulmonary fibrosis, granulomatous colitis, immunodeficiency, or abnormal storage of fatty-like substance (ceroid lipofuscin) in various tissues of the body.

There are eleven different types of HPS, which can be stratified by their signs and symptoms and underlying genetic cause. Types 1 and 4 are the most severe forms of the disorder. Types 1, 2, and 4 are the only types associated with pulmonary fibrosis. Individuals with type 3, 5, or 6 have the mildest symptoms. Very few is known about the signs, symptoms, and severity of types 7, 8, 9, 10 and 11.

The test covers the known genetic causes of HPS. The disease is inherited in an autosomal recessive pattern.

HPS is a rare disorder in most populations and is estimated to affect 1: 500 000 to 1 000 000 individuals worldwide. Type 1 is more common in northwest Puerto Rico where about 1: 1800 people are affected. Type 3 is common in people from central Puerto Rico. Groups of affected individuals have been identified in many other regions, including India, Japan, the United Kingdom, and Western Europe. HPS is the third most prevalent form of albinism.

References:
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. https://www.ncbi.nlm.nih.gov/books/NBK1287/. 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
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

List of diseases covered by Oculocutaneous Albinism, Ocular Albinism, Hermansky-Pudlak Syndrome, Chediak-Higashi Syndrome NGS panel

List of diseases covered by Oculocutaneous Albinism, Ocular Albinism, Hermansky-Pudlak Syndrome, Chediak-Higashi Syndrome NGS panel

Gene Condition
AP3B1 Hermansky-Pudlak syndrome 2
AP3D1 Hermansky-Pudlak syndrome 10
BLOC1S3 Hermansky-Pudlak syndrome 8
BLOC1S5 Hermansky-Pudlak syndrome
BLOC1S6 Hermansky-pudlak syndrome 9
DTNBP1 Hermansky-Pudlak syndrome 7
GPR143 Nystagmus 6, congenital, X-linked;
Ocular albinism, type I, Nettleship-Falls type
HPS1 Hermansky-Pudlak syndrome 1
HPS3 Hermansky-Pudlak syndrome 3
HPS4 Hermansky-Pudlak syndrome 4
HPS5 Hermansky-Pudlak syndrome 5
HPS6 Hermansky-Pudlak syndrome 6
LRMDA Albinism, oculocutaneous, type VII
LYST Chediak-Higashi syndrome
MC1R Skin/hair/eye pigmentation 2, blond hair/fair skin;
Albinism, oculocutaneous, type II, modifier of;
Melanoma, cutaneous malignant, 5;
OCA2 Albinism, oculocutaneous, type II
SLC24A5 Albinism, oculocutaneous, type VI
SLC45A2 Albinism, oculocutaneous, type IV
TYR Albinism, oculocutaneous, type IA;
Albinism, oculocutaneous, type IB;
Waardenburg syndrome/albinism, digenic
TYRP1 Albinism, oculocutaneous, type III