Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0009319 (colitis)
 19,384 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a storage pool deficiency due to an absence of platelet dense bodies. Lysosomal ceroid lipofuscinosis, pulmonary fibrosis and granulomatous colitis are occasional manifestations of the disease. HPS occurs with a frequency of one in 1800 in north-west Puerto Rico due to a founder effect. Several non-Puerto Rican patients also have mutations in HPS1, which produces a protein of unknown function. Another gene, ADTB3A, causes HPS in the pearl mouse and in two brothers with HPS-2 (refs. 11,12). ADTB3A encodes a coat protein involved in vesicle formation, implicating HPS as a disorder of membrane trafficking. We sought to identify other HPS-causing genes. Using homozygosity mapping on pooled DNA of 6 families from central Puerto Rico, we localized a new HPS susceptibility gene to a 1.6-cM interval on chromosome 3q24. The gene, HPS3, has 17 exons, and a putative 113.7-kD product expected to reveal how new vesicles form in specialized cells. The homozygous, disease-causing mutation is a large deletion and represents the second example of a founder mutation causing HPS on the small island of Puerto Rico. We also present an allele-specific assay for diagnosing individuals heterozygous or homozygous for this mutation.
 ...
PMID:Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico. 1145 88

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder causing oculocutaneous albinism and a platelet storage pool deficiency, reflecting defective biosynthesis and/or processing of melanosomes and platelet dense bodies. Four human genes (HPS1, ADTB3A, HPS3, HPS4) are associated with four subtypes of HPS. The most common is HPS-1. A 16-bp duplication in exon 15 of the HPS1 gene causes HPS-1 in 450 northwest Puerto Rican patients; 13 other HPS1 mutations have been reported in non-Puerto Rican patients. We screened 26 HPS patients, who lacked a molecular diagnosis, for HPS1 defects and identified six patients with six different HPS1 mutations. Four novel mutations were discovered, including the first HPS1 missense mutation, 922T>C, in exon 8. This mutation, along with 624delG in exon 6, preserve RNA transcription, while 561delC in exon 5 and [1581delA;1594C>A] in exon 14 produce no RNA on northern blot. One of six adult patients developed pulmonary fibrosis, and two patients ages 16 and 17 have granulomatous colitis. These complications are common among Puerto Rican HPS-1 patients but have not appeared in HPS-2 or HPS-3 patients. The diagnosis of HPS-1, available only on molecular grounds, has important prognostic and treatment implications.
 ...
PMID:Hermansky-Pudlak syndrome type 1: gene organization, novel mutations, and clinical-molecular review of non-Puerto Rican cases. 1244 88

The disorders known as Hermansky-Pudlak syndrome (HPS) are a group of genetic diseases resulting from abnormal formation of intracellular vesicles. In HPS, dysfunction of melanosomes results in oculocutaneous albinism, and absence of platelet dense bodies causes a bleeding diathesis. In addition, some HPS patients suffer granulomatous colitis or fatal pulmonary fibrosis, perhaps due to mistrafficking of a subset of lysosomes. The impaired function of specific organelles indicates that the causative genes encode proteins operative in the formation of certain vesicles. Four such genes, HPS1, ADTB3A, HPS3, and HPS4, are associated with the four known subtypes of HPS, i.e. HPS-1, HPS-2, HPS-3, and HPS-4. ADTB3A codes for the beta 3 A subunit of adaptor complex-3, known to assist in vesicle formation from the trans-Golgi network or late endosome. However, the functions of the HPS1, HPS3, and HPS4 gene products remain unknown. These three genes arose with the evolution of mammals and have no homologs in yeast, reflecting their specialized function. In contrast, all four known HPS-causing genes have homologs in mice, a species with 14 different models of HPS, i.e. hypopigmentation and a platelet storage pool deficiency. Pursuit of the mechanism of mammalian vesicle formation and trafficking, impaired in HPS, relies upon investigation of these mouse models as well as studies of protein complexes involved in yeast vacuole formation.
 ...
PMID:Hermansky-Pudlak syndrome: vesicle formation from yeast to man. 1245 82

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder of oculocutaneous albinism and bleeding attributable to storage-pool-deficient platelets. Although at least 14 mouse models of HPS exist, the human disorders that comprise HPS, i.e., HPS-1, HPS-2, HPS-3, and HPS-4, are recognized to result from mutations in four genes, viz., HPS1, ADTB3A, HPS3, and HPS4, respectively. To characterize further the recently identified HPS-4 disease on molecular and clinical grounds, we first identified the genomic organization of HPS4, located on chromosome 22q11.2-q12.2, including its intron/exon boundaries. We found that HPS4 produces at least two alternatively spliced mRNA transcripts that differ at their 5'-ends. Next, we performed an extensive analysis of 22 unassigned HPS patients (i.e., not having HPS-1, HPS-2, or HPS-3 disease). Using single-strand conformation polymorphism, we determined that seven of the 22 patients had HPS-4. In these seven individuals, we identified five different HPS4 mutations, including one frameshift insertion, one missense, and three nonsense mutations. Three alleles in two patients contained the previously reported Q698insAAGCA frameshift. Three HPS4 mutations were newly described. Four alleles in three patients contained R217X, and two siblings were compound heterozygotes for E138X and E222X. Clinically, our HPS-4 patients exhibited iris transillumination, variable hair and skin pigmentation, absent platelet dense bodies, and occasional pulmonary fibrosis and granulomatous colitis, a severe phenotype similar to that of patients with HPS-1.
 ...
PMID:Hermansky-Pudlak syndrome type 4 (HPS-4): clinical and molecular characteristics. 1266 4

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a platelet storage pool deficiency. Some patients also develop fatal pulmonary fibrosis and some have granulomatous colitis. Six human genes HPS1, ADB3A, HPS3, HPS4, HPS5, and HPS6 have been identified as cause of the six known subtypes of HPS. While there exist nearly 500 Puerto Rican and non-Puerto Rican HPS-1 patients, very few HPS-4 patients have been reported, and most of these have not been described in detail. We now delineate the clinical characteristics of an HPS-4 patient homozygous for a novel HPS-4 mutation, P685delC. The patient, the first individual with HPS reported from Sri Lanka, had severe pulmonary fibrosis, typical of HPS-1 disease, without granulomatous colitis. We conclude that pulmonary fibrosis occurs as part of HPS-4 and that HPS should be considered in all ethnic groups.
 ...
PMID:Hermansky-Pudlak syndrome type 4 in a patient from Sri Lanka with pulmonary fibrosis. 1510 12

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction. A subset of patients also show ceroid deposition, which can result in pulmonary fibrosis or granulomatous colitis. Whether this colitis may be considered Crohn's disease is under debate. We report a case of a patient with HPS associated with inflammatory bowel disease which affected the distal small bowel but not the colon. Ileitis was severe, and recurred rapidly after surgery. Search for mutations in HPS1, ADTB3A, HPS3, HPS4 and for CARD15 were negative. Symptoms and ileal ulcerations which recurred after surgery were successfully treated with azathioprine and infliximab.
 ...
PMID:Ileal Crohn's disease in a woman with Hermansky-Pudlak syndrome. 1673 90

Hermansky-Pudlak syndrome (HPS), first described in 1959, is a rare form of syndromic oculocutaneous albinism associated with bleeding diathesis and in some cases pulmonary fibrosis and granulomatous colitis. All 10 HPS types are caused by defects in vesicle trafficking of lysosome-related organelles (LRO) proteins. The HPS5 protein associates with HPS3 and HPS6 to form the biogenesis of lysosome-related organelles complex-2 (BLOC-2). Here, we report the clinical and genetic data of 11 patients with HPS-5 analyzed in our laboratory. We report 11 new pathogenic variants. The 11 patients present with ocular features that are typical for albinism, with mild hypopigmentation, and with no other major complication, apart from a tendency to bleed. HPS-5 therefore appears as a mild form of HPS, which is often clinically undistinguishable from mild oculocutaneous or ocular forms of albinism. Molecular analysis is therefore required to establish the diagnosis of this mild HPS form, which has consequences in terms of prognosis and of clinical management of the patients.
 ...
PMID:Clinico-molecular analysis of eleven patients with Hermansky-Pudlak type 5 syndrome, a mild form of HPS. 2864 Sep 47