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Oculocutaneous Albinism
Oculocutaneous
albinism (OCA) is a heterogeneous group of congenital disorders characterized
by hypopigmentation of skin, hair, and eyes associated with other developmental
ocular defects. OCA patients are often considered as legally blind and in
India, it is one of the 4 major causes of childhood blindness. Long-term sun
exposure greatly increases the risk of skin damage and an aggressive form of
skin cancer called melanoma, in people with this condition. Mutations in genes
regulating the multistep process of melanin biosynthesis cause this spectrum of
disorders. The four classical types of oculocutaneous albinism are designated
as OCA1 (OCA1A:
MIM: 203100 and
OCA1B:
MIM: 606952),
OCA2 (
MIM: 203200),
OCA3 (
MIM: 203290)
and OCA4 (
MIM: 606574)
caused by TYR,
OCA2, TYRP1 and
SLC45A2 genes, respectively. OCA1 is characterized by white hair, very
pale skin, and light-colored irises. OCA2 and OCA4 have overlapping clinical
features (a creamy white color and hair may be light yellow, blond, or light
brown) that are generally less severe than OCA1. OCA3 affected individuals have
reddish-brown skin, ginger or red hair and hazel or brown irises with milder
vision abnormalities than the other forms of OCA. Overall, an estimated 1 in
20,000-30,000 people worldwide are born with oculocutaneous albinism however,
the frequency differs from country to country. In India, OCA1 is the most
prevalent type of OCA followed by OCA2.
This database presently holds the relevant data for OCA1, OCA2, OCA3 and OCA4.
Hermansky-Pudlak Syndrome (
MIM: 203300)
It
is a rare autosomal recessive disorder characterised by oculocutaneous
albinism, bleeding, and lysosomal ceroid storage result from defects of
multiple cytoplasmic organelles: melanosomes, platelet-dense granules, and
lysosomes. Hermansky-Pudlak syndrome (HPS) can be caused by mutation in several
genes: HPS1 (
MIM: 604982),
HPS3 (
MIM: 606118),
HPS4 (
MIM: 606682),
HPS5 (
MIM: 607521),
and HPS6 (
MIM: 607522).
HPS2 (
MIM: 608233),
AP3B1 (
MIM: 603401),
DTNBP1 (
MIM: 607145)
and BLOC1S3 (
MIM: 609762).
The
database presently holds the data for HPS1 only.
H syndrome (
MIM: 602782)
H
syndrome is a recently reported autosomal-recessive disorder characterized by
cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart
anomalies, hearing loss, hypogonadism, short stature, hallux valgus, and fixed
flexion contractures of the toe joints and the proximal interphalangeal joints.
It is caused by mutations in the SLC29A3
gene, which encodes the equilibrative nucleoside transporter hENT3.
Dyskeratosis congenita (
MIM: 305000)
The
disease mainly affects the integumentary system with a major
consequence being anomalies of the bone marrow. The disorder is
characterised by premature aging with cutaneous pigmentation, dystrophy of the
nails, leukoplakia of the oral mucosa, continuous lacrimation due to atresia of
the lacrimal ducts, often thrombocytopenia, anemia, and in most cases
testicular atrophy. Only males are affected in a pattern consistent with
X-linked recessive inheritance as a result of one or more mutations in the long
arm of the X chromosome in the gene DKC1.
This
may result in specific issues related to dysfunctional rRNA and perhaps a
graver phenotype.
Incontinentia pigmenti (
MIM: 308300 )
Incontinentia pigmenti
is a X-linked dominant genodermatosis and is usually lethal prenatally in
males. However in affected females it causes highly variable abnormalities of
the skin, hair, nails, teeth, eyes, and central nervous system with extremely
skewed X-inactivation. The prominent skin signs occur in 4 classic cutaneous
stages: perinatal inflammatory vesicles, verrucous patches, a distinctive
pattern of hyperpigmentation, and dermal scarring. Familial
incontinentia pigmenti is caused by mutations in the NEMO gene.
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