Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Dutch kindred with the Hermansky-Pudlak syndrome (HPS) is described. We show for the first time evidence of a lowered platelet 5-hydroxytryptamine content in obligate heterozygotes. Platelet ATP and ADP levels and ATP/ADP ratio were normal in these patients. Platelet aggregation with ADP, collagen and adrenaline was within the normal range. In contrast to the homozygous HPS patients the heterozygotes are normally pigmented and none has diaphanous irides, nystagmus or a bleeding tendency. All homozygous HPS patients have the typical triad of oculocutaneous albinism, pigmented macrophages in the bone marrow and a bleeding disorder, based on a platelet dysfunction. The platelets showed the typical characteristics of a storage pool deficiency. Their platelet factor 3 availability was decreased and the aggregation patterns showed an absent second wave with ADP, adrenaline and absent collagen aggregation. Platelet ADP levels were strongly decreased in all homozygous HPS patients, whereas ATP was lowered only in 3 out of 6 HPS patients. The 5-hydroxytryptamine content of their platelets was very low (15-20% of normal).
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PMID:The Hermansky-Pudlak syndrome. Evidence for a lowered 5-hydroxytryptamine content in platelets of heterozygotes. 84 98

Oculocutaneous albinism (OCA) is an inherited condition characterized by hypopigmentation of the skin, hair, and eyes. Ocular involvement is often severe with photophobia, decreased visual acuity due to foveal hypoplasia, nystagmus, and strabism secondary to defective routing of optic axons in the chiasma. Cutaneous hypopigmentation is responsible for diminished photoprotection that places patients at increased risk for skin cancers. OCA also occurs in a number of life-threatening conditions, including Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Griscelli-Prunieras syndrome. Most cases of OCA are inherited on an autosomal recessive basis. Several mutations have recently been identified in type I OCA or "tyrosinase-negative" OCA. Identification of other genetic abnormalities will probably occur in the future and will lead to more accurate classification of OCA syndromes.
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PMID:[Oculocutaneous albinism]. 141 62

A young girl with ocular albinism and the Hermansky-Pudlak syndrome is described. Ocular albinism generally occurs in males. In this condition, the pigmentation of the skin and hair is nearly normal, and the melanin pigment abnormality is limited to the eyeballs. The chief complaints are visual disturbance, nystagmus, and photophobia. A 3-year-old girl was recently brought to our hospital with nystagmus, which she had exhibited since the age of 1 year. Funduscopy resulted in a diagnosis of ocular albinism. Further investigations, specifically, microscopy of her platelets, led us to conclude that she had Hermansky-Pudlak syndrome.
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PMID:A girl with Hermansky-Pudlak syndrome. 187 48

Flash visual evoked potentials (F. VEPs) and electroretinograms (ERGs) were recorded in a total of 20 young children with albinism (age range 5 months to 11 years, mean 4 years). All recordings were made without sedation. There were 13 oculocutaneous cases (one with Hermansky-Pudlak syndrome) and seven ocular albinos. Monocular flash stimulation commonly elicited an asymmetrical occipital VEP distribution with a well lateralised component at around 80 ms which was of opposite polarity in a comparison of VEPs from each eye. None of the normally pigmented matched controls or obligate female carriers showed this anomalous distribution. The albino electroretinogram, compared with controls, recorded under fully darkened conditions had a significantly larger a wave and significantly shorter latencies for both a and b waves. The accentuated ERG and asymmetrical VEP recorded in infants and young children with albinism permits distinction of these patients from those with congenital cone dysfunction and idiopathic nystagmus, with whom they may be confused by a clinical examination only.
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PMID:Albinism in childhood: a flash VEP and ERG study. 232 6

Prospective ophthalmic evaluation was performed in 20 individuals with Hermansky-Pudlak syndrome, a type of oculocutaneous albinism with an associated deficiency of dense bodies in platelets. The extent of visual impairment and the possible relationship to the degree of hypopigmentation were studied. All patients showed nystagmus, visual acuity ranged from 20/60 to 20/400, and correction of refractive error provided a mild improvement in vision. Iris pigmentation varied in amount and did not correlate with the visual acuity measurement. Foveal hypoplasia was found in all patients, but variability in macular transparency and vascular architecture was noted. Visual-evoked potentials performed in 11 patients demonstrated excessive decussation of optic fibers. Recognition of this form of oculocutaneous albinism is important because of the associated pulmonary, gastrointestinal, renal, and cardiac manifestations of Hermansky-Pudlak syndrome.
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PMID:Hermansky-Pudlak syndrome. Ophthalmic findings. 317 14

We studied the case of a young patient affected by a Hermansky-Pudlak syndrome: oculocutaneous albinism of variable intensity with essentially an haemorrhagic diathesis due to a "pool vide" thrombopathy. In beginning the only obvious symptom was a nystagmus and an ocular albinism. Cerebrospinal hemorrhage has up to now never been reported to our knowledge. Healthy carriers can be detected by ophthalmological examination and hematological coagulation tests. Albinos must benefit of systematical coagulation tests in order to prevent drug induced haemorrhagic accident.
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PMID:[Meningeal hemorrhage and Hermansky-Pudlak syndrome]. 381 28

Hermansky-Pudlak syndrome (HPS) consists of ocu-locutaneous albinism, a platelet storage-pool deficiency, and ceroid lipofuscinosis. In a recent report on the cloning of an HPS gene, all 22 Puerto Rican HPS patients were homozygous for a 16-bp duplication in exon 15. This presumably reflected a founder effect for the HPS mutation in Puerto Rico. Nevertheless, we ascertained two individuals from central Puerto Rico who lacked the 16-bp duplication, exhibited significant amounts of normal-size HPS mRNA by northern blot analysis, and had haplotypes in the HPS region that were different from the haplotype of every 16-bp-duplication patient. Moreover, these two individuals displayed no mutations in their cDNA sequences, throughout the entire HPS gene. Both patients exhibited pigment dilution, impaired visual acuity, nystagmus, a bleeding diathesis, and absent platelet dense bodies, confirming the diagnosis of HPS. These findings indicate that analysis of Puerto Rican patients for the 16-bp duplication in HPS cannot exclude the diagnosis of HPS. In addition, HPS most likely displays locus heterogeneity, consistent with the existence of several mouse strains manifesting both pigment dilution and a platelet storage-pool deficiency.
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PMID:Evidence for locus heterogeneity in Puerto Ricans with Hermansky-Pudlak syndrome. 934 5

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by pigment dilution, nystagmus, decreased visual acuity, a bleeding diathesis, and lysosomal accumulation of ceroid lipofuscin. Electron microscopic evidence demonstrating lack of platelet-dense bodies provides the sine qua non for diagnosing HPS. Ceroid lipofuscinosis is considered to cause several serious complications, including progressive pulmonary fibrosis leading to death in the fourth or fifth decades. Currently, only symptomatic treatment can be offered. Although rare in the general population, HPS occurs in northwest Puerto Rico with a prevalence of 1 in 1800. HPS1, the first gene found to be responsible for HPS, was mapped to chromosome 10q23 and subsequently isolated and sequenced. It consists of 20 exons encoding a 700-amino acid, 79.3-kDa peptide with no homology to any known protein. All 10 HPS1 mutations reported to date, including the 16-bp duplication found in all northwest Puerto Rican patients, result in truncated proteins. The two mutations in the mouse pale ear gene (ep), which is the murine homology of HPS1, cause similarly truncated proteins. The pathologic nature of these truncation mutations may result from unstable mRNA. However, in combination with the absence of any disease-causing missense mutations, it may indicate that the C-terminus of the HPS1 peptide is functionally important. The disorder HPS displays locus heterogeneity, consistent with the existence of 14 mouse strains manifesting both hypopigmentation and a platelet storage pool deficiency. Two mouse models, pearl and mocha, have mutations in the beta3A and delta subunits of the adaptor-3 complex, respectively. This suggests that defective vesicular trafficking, specifically cargo packaging, vesicle formation, vesicle docking, or membrane fusion, may comprise the basic defect in HPS. Studies of the proteins involved in intercompartmental transport for melanosomes, platelet-dense bodies, and lysosomes should lead to a better understanding of the mechanisms of organellogenesis and to more effective therapies for HPS.
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PMID:Hermansky-Pudlak syndrome: models for intracellular vesicle formation. 978

Albinism, caused by a deficiency of melanin pigment in the skin, hair, and eye (oculocutaneous albinism [OCA]), or primarily in the eye (ocular albinism [OA]), results from mutations in genes involved in the biosynthesis of melanin pigment. The lack of melanin pigment in the developing eye leads to fovea hypoplasia and abnormal routing of the optic nerves. These changes are responsible for the nystagmus, strabismus, and reduced visual acuity common to all types of albinism. Mutations in six genes have been reported to be responsible for different types of oculocutaneous and ocular albinism, including the tyrosinase gene (TYR) and OCA1 (MIM# 203100), the OCA2 gene and OCA2 (MIM# 203200), the tyrosinase-related protein-1 gene (TYRP1) and OCA3 (MIM# 203290), the HPS gene and Hermansky-Pudlak syndrome (MIM# 203300), the CHS gene (CHS1), and Chediak-Higashi syndrome (MIM# 214500), and the X-linked ocular albinism gene and OA1 (MIM#300500). The function of only two of the gene products is known tyrosinase and tyrosinase-related protein-1 both of which are enzymes in the melanin biosynthetic pathway. Continued mutational analysis coupled with function/structure studies should aid our understanding of the function of the remaining genes and their role in albinism. Mutation and polymorphism data on these genes are available from the International Albinism Center Albinism Database web site (http://www.cbc.umn.edu/tad).
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PMID:Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. 1009 67

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive inherited disease consisting of (1) partial oculocutaneous albinism (with nystagmus, strabism, and visual acuity loss), (2) platelet storage pool deficiency (with bleeding diathesis), and (3) disorder of "ceroid" metabolism with a multisystem tissue lysosomal ceroid deposition. HPS is less uncommon in Puerto Rico, where the most important studies have been performed, but is a very rare disease in Europe. HPS basic defect remains unknown, even if an HPS-causing gene was identified in chromosome segment 10q23-q23.3, and several mutations have been reported. The aim of this article is to discuss, on the basis of a review of relevant literature, a new familial HPS clinical variant observed in 2 young sisters (aged 16 and 23 years old, respectively), characterized by the typical symptoms of this syndrome. Our patients also suffered from diffuse interstitial pulmonary disease and an unexpectedly increased platelet aggregation and were prone to bacterial infections. Interestingly, we observed urinary tract abnormality in the younger HPS sister and a porencephalic cyst in the older HPS sister; both of these developmental defects have been reported in the Cross syndrome (or oculocerebral hypopigmentation syndrome). It seems that in our patients, an overlapping of the phenotypic manifestations of different rare syndromes may be present. The presence of ceroid-like autofluorescent material in urinary sediment together with the histologic aspects and the autofluorescence of oral mucosa biopsy are consistent with a ceroid-like lipofuscin storage. HPS should be carefully tested for in suspected cases to prevent the severe visual impairment, rapidly progressive pulmonary fibrosis, and other complications associated with this disorder.
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PMID:A clinical variant of familial Hermansky-Pudlak syndrome. 1282 64


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