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Albinism
- Hermansky-Pudlak syndrome
Hermansky-Pudlak syndrome (HPS) is a rare disorder which has several
features including; lack of hair, skin and eye color, prolonged
bleeding, and problems with lysosomal ceroid storage. These symptoms
occur due to defects in the melanosome, platelet-dense granule,
and lysosome organelles of cells found in various cell types.
Hermansky-Pudlak syndrome is a genetic autosomal recessive disorder
so it runs in families. There are 3 subtypes of Hermansky-Pudlak
syndrome. HPS1 involves a mutation in the HPS1 gene on chromosome
10. HPS2 is caused by mutation in a gene on chromosome 5 encoding
the beta-3A subunit of a protein complex called AP3. HPS3 involves
a defect in a gene on chromosome 3.
Hermansky-Pudlak syndrome is probably the most common single gene
disorder found in people of Puerto Rican ancestry. Hermansky-Pudlak
syndrome has a frequency of about 1 in 1,800 Puerto Ricans which
suggests that the frequency of Puerto Ricans carrying the gene is
about 1 in 21 (Wildenberg 1995). Hermansky-Pudlak syndrome is also
found in isolated pockets where the population is relatively inbred
such as a mountain village high in the Swiss Alps (Schallreuter
1993).
Albinism
- Chediak-Higashi syndrome
Chediak-Higashi syndrome (CHS) is a related disorder of Hermansky-Pudlak
syndrome in which similar defects occur. However, this syndrome
is different from Hermansky-Pudlack syndrome because there are significant
changes in the numbers and activity of white blood cells. So the
dominant feature of Chediak-Higashi syndrome is that affected individuals
are immune deficient.
The symptoms include; a partial lack of hair, skin and eye color,
increased susceptibility to infections, deficient natural killer
cell activity, susceptibility to malignant lymphoma, and the presence
of large intracytoplasmic granulations in various cell types. The
symptoms are so severe that most people with Chediak-Higashi syndrome
die at an early age.
Chediak-Higashi syndrome is a severe autosomal recessive immune
deficiency disorder. There are at least 8 known gene allele defects
that can cause Chediak-Higashi syndrome and it is quite possible
that there are others that have yet to be identified. Chediak-Higashi
syndrome arises due to an abnormal intracellular protein transport
to, and from, the lysosome organelles in cells.
Albinism
- references
- Oetting WS, King RA. Molecular basis of
albinism: mutations and polymorphisms of pigmentation genes associated
with albinism. Hum Mutat. 1999;13(2):99-115.
- Oh J, Ho L, Ala-Mello S, Amato D, Armstrong
L, Bellucci S, Carakushansky G, Ellis JP, Fong CT, Green JS, Heon
E, et al. Mutation analysis of patients with Hermansky-Pudlak
syndrome: a frameshift hot spot in the HPS gene and apparent locus
heterogeneity. Am J Hum Genet. 1998 Mar;62(3):593-8.
- Anikster Y, Huizing M, White J, Shevchenko
YO, Fitzpatrick DL, Touchman JW, Compton JG, Bale SJ, Swank RT,
Gahl WA, Toro JR. Mutation of a new gene causes a unique form
of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto
Rico. Nat Genet. 2001 Aug;28(4):376-80.
- Dell'Angelica EC, Shotelersuk V, Aguilar
RC, Gahl WA, Bonifacino JS. Altered trafficking of lysosomal proteins
in Hermansky-Pudlak syndrome due to mutations in the beta 3A subunit
of the AP-3 adaptor. Mol Cell. 1999 Jan;3(1):11-21.
- Oetting WS. Albinism. Curr Opin Pediatr.
1999 Dec;11(6):565-71.
- Sturm RA, Box NF, Ramsay M. Human pigmentation
genetics: the difference is only skin deep. Bioessays. 1998 Sep;20(9):712-21.
- Lyle WM, Sangster JO, Williams TD. Albinism:
an update and review of the literature. J Am Optom Assoc. 1997
Oct;68(10):623-45.
- Orlow SJ. Albinism: an update. Semin Cutan
Med Surg. 1997 Mar;16(1):24-9.
- Barbosa MD, Barrat FJ, Tchernev VT, Nguyen
QA, Mishra VS, Colman SD, Pastural E, Dufourcq-Lagelouse R, Fischer
A, Holcombe RF, Wallace MR, Brandt SJ, de Saint Basile G, Kingsmore
SF. Identification of mutations in two major mRNA isoforms of
the Chediak-Higashi syndrome gene in human and mouse. Hum Mol
Genet. 1997 Jul;6(7):1091-8.
- Oetting WS, Brilliant MH, King RA. The
clinical spectrum of albinism in humans. Mol Med Today. 1996 Aug;2(8):330-5.
- Barbosa MD, Nguyen QA, Tchernev VT, Ashley
JA, Detter JC, Blaydes SM, Brandt SJ, Chotai D, Hodgman C, Solari
RC, Lovett M, Kingsmore SF. Identification of the homologous beige
and Chediak-Higashi syndrome genes. Nature. 1996 Jul 18;382(6588):262-5.
- Fukai K, Oh J, Frenk E, Almodovar C, Spritz
RA. Linkage disequilibrium mapping of the gene for Hermansky-Pudlak
syndrome to chromosome 10q23.1-q23.3. Hum Mol Genet. 1995 Sep;4(9):1665-9.
- Wildenberg SC, Oetting WS, Almodovar C,
Krumwiede M, White JG, King RA. A gene causing Hermansky-Pudlak
syndrome in a Puerto Rican population maps to chromosome 10q2.
Am J Hum Genet. 1995 Oct;57(4):755-65.
- Schallreuter KU, Frenk E, Wolfe LS, Witkop CJ,
Wood JM. Hermansky-Pudlak syndrome in a Swiss population. Dermatology.
1993;187(4):248-56.
- Garay SM, Gardella JE, Fazzini EP, Goldring
RM. Hermansky-Pudlak syndrome. Pulmonary manifestations of a ceroid
storage disorder. Am J Med. 1979 May;66(5):737-47.
- Logan LJ, Rapaport SI, Maher I. Albinism
and abnormal platelet function. N Engl J Med. 1971 Jun 17;284(24):1340-5.
- Windhorst DB, Zelickson AS, Good RA. A
human pigmentary dilution based on a heritable subcellular structural
defect--the Chediak-Higashi syndrome. J Invest Dermatol. 1968
Jan;50(1):9-18.
- Hermansky F, Pudlak P. Albinism associated
with hemorrhagic diathesis and unusual pigmented reticular cells
in the bone marrow: report of two cases with histochemical studies.
Blood 1959;14:62-169.
- Chediak M. Nouvelle anomalie leucocytaire
de caractere constitutionnel et familial. Rev Hemat. 1952;7:362-367.
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