Subject(s)
Albinism, Oculocutaneous/diagnosis , Biomarkers , Hermanski-Pudlak Syndrome/diagnosis , Melanosis/diagnosis , Skin Pigmentation , Albinism, Oculocutaneous/ethnology , Albinism, Oculocutaneous/genetics , Asian People/ethnology , Carrier Proteins/genetics , Child , DNA Mutational Analysis , Female , Guanine Nucleotide Exchange Factors , Hermanski-Pudlak Syndrome/ethnology , Hermanski-Pudlak Syndrome/genetics , Humans , India/epidemiology , Intracellular Signaling Peptides and Proteins , Male , Membrane Proteins/genetics , Mutation , Pedigree , Polymerase Chain Reaction , Proteins/geneticsABSTRACT
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive genetic disorder characterized by oculocutaneous albinism and a bleeding diathesis due to platelet dysfunction. More than 50% of cases worldwide are diagnosed on the Caribbean island of Puerto Rico. Genetic testing plays a growing role in diagnosis; however, not all patients with HPS have identified genetic mutations. In Puerto Rico, patients with HPS are often identified shortly after birth by their albinism, although the degree of hypopigmentation is highly variable. Ten subtypes have been described. Patients with HPS-1, HPS-2, and HPS-4 tend to develop pulmonary fibrosis in Puerto Rico; 100% of patients with HPS-1 develop HPS-PF. HPS-PF and idiopathic pulmonary fibrosis are considered similar entities (albeit with distinct causes) because both can show similar histological disease patterns. However, in contrast to idiopathic pulmonary fibrosis, HPS-PF manifests much earlier, often at 30-40 years of age. The progression of HPS-PF is characterized by the development of dyspnea and increasingly debilitating hypoxemia. No therapeutic interventions are currently approved by the U.S. Food and Drug Administration for the treatment of HPS and HPS-PF. However, the approval of two new antifibrotic drugs, pirfenidone and nintedanib, has prompted new interest in identifying drugs capable of reversing or halting the progression of HPS-PF. Thus, lung transplantation remains the only potentially life-prolonging treatment. At present, two clinical trials are recruiting patients with HPS-PF to identify biomarkers for disease progression. Advances in the diagnosis and management of these patients will require the establishment of multidisciplinary centers of excellence staffed by experts in this disease.
Subject(s)
Hermanski-Pudlak Syndrome/complications , Hermanski-Pudlak Syndrome/ethnology , Pulmonary Fibrosis/therapy , Animals , Biomarkers , Disease Progression , Hispanic or Latino , Humans , Indoles/therapeutic use , Lung Transplantation , Membrane Proteins/genetics , Mice , Mutation , Puerto Rico/ethnology , Pyridones/therapeutic use , Randomized Controlled Trials as Topic , Tomography, X-Ray ComputedABSTRACT
Oculocutaneous albinism (OCA) is a heterogeneous recessive disorder with hypopigmentation in the skin, hair, and eyes. At least 16 genes have been identified as causative genes for human OCA. No comprehensive analysis has been conducted to study the spectral distribution of OCA in Chinese patients. We screened 127 unrelated and unselected Chinese OCA patients for mutations in the TYR, OCA2, TYRP1, SLC45A2, and HPS1 genes. We found that the spectrum of mutational genes and alleles of OCA is population specific. OCA1 is the most common (70.1% of cases) form of Chinese OCA, whereas OCA2, OCA4, and HPS1 account for 10.2%, 12.6%, and 1.6%, respectively. No apparent pathological mutation of TYRP1 has been found. Thirty-eight previously unreported mutational alleles were identified from these OCA patients and were not found in 100 nonalbinism subjects. Of the TYR mutational alleles, 81.1% were clustered on exons 1 and 2. Ten common alleles account for 74.6% of the mutational TYR alleles in Chinese OCA1 patients. The p.D160H allele accounts for 55.6% of the mutational SLC45A2 alleles in Chinese OCA4 patients. These results provide useful information for the establishment of an optimized strategy of gene diagnosis and genetic counseling of Chinese OCA patients.
Subject(s)
Albinism, Oculocutaneous/ethnology , Albinism, Oculocutaneous/genetics , Asian People/genetics , Asian People/statistics & numerical data , Polymorphism, Single Nucleotide , Alleles , Antigens, Neoplasm/genetics , China/epidemiology , DNA Mutational Analysis , Female , Genetic Predisposition to Disease/ethnology , Genetic Testing , Hermanski-Pudlak Syndrome/ethnology , Hermanski-Pudlak Syndrome/genetics , Humans , Male , Membrane Glycoproteins/genetics , Membrane Proteins/genetics , Membrane Transport Proteins/genetics , Monophenol Monooxygenase/genetics , Oxidoreductases/genetics , PrevalenceSubject(s)
Asian People/genetics , Hermanski-Pudlak Syndrome/genetics , Membrane Proteins/genetics , Sequence Deletion , Child, Preschool , China , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Hermanski-Pudlak Syndrome/ethnology , Hermanski-Pudlak Syndrome/pathology , Homozygote , Humans , Pedigree , PhenotypeABSTRACT
Hermansky-Pudlak syndrome is an autosomal recessive disorder commonly found in individuals of Puerto Rican ancestry. We present 2 cases of familial pulmonary fibrosis in 2 Mexican sisters with Hermansky-Pudlak syndrome. Pulmonary fibrosis was biopsy-proven in 1 of the patients. This report shows that Hermansky-Pudlak syndrome may occur in individuals of Mexican ancestry.
Subject(s)
Hermanski-Pudlak Syndrome/complications , Pulmonary Fibrosis/etiology , Fatal Outcome , Female , Genes, Recessive , Hermanski-Pudlak Syndrome/diagnosis , Hermanski-Pudlak Syndrome/ethnology , Hermanski-Pudlak Syndrome/genetics , Hermanski-Pudlak Syndrome/pathology , Humans , Lung/pathology , Mexico , Middle Aged , SiblingsABSTRACT
Hermansky-Pudlak syndrome (HPS) is a rare disorder characterised by oculocutaneous albinism, a bleeding tendency, and lipofuscinosis. This retrospective study reviews the clinical history and haematological features of 23 cases of HPS. Information was gathered from patient notes and by direct interview. Thirteen of the 23 children were of Turkish origin, 12 being members of four kindreds from the Turkish/Kurdish border. Four children originated from Pakistan. Haemorrhage was uncommon; two experienced significant bleeding (intracranial and retinal haemorrhage in one and menorrhagia in another), and twelve minor symptoms. Results of laboratory evaluation of platelet function were not predictive of bleeding; in particular the PFA-100 analyser was not sensitive to the HPS defect. The most sensitive test of platelet fuction was quantitation of platelet nucleotides. The occurrence of Turkish and Pakistani kindreds with HPS is novel and follow up for long term complications described in Puerto Rican patients as well as genetic analysis is ongoing.
Subject(s)
Hermanski-Pudlak Syndrome/ethnology , Bleeding Time , Child , Female , Hemorrhagic Disorders/ethnology , Hemorrhagic Disorders/genetics , Hermanski-Pudlak Syndrome/genetics , Hermanski-Pudlak Syndrome/physiopathology , Humans , Male , Pakistan/ethnology , Pedigree , Platelet Aggregation/genetics , Turkey/ethnologyABSTRACT
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA), platelet storage pool deficiency, and ceroid lipofuscin deposition. Sequelae including pulmonary fibrosis, colitis, and hemorrhagic diathesis can impact obstetric management. An 18-year-old primigravida with OCA was diagnosed during pregnancy with Hermansky-Pudlak syndrome by DNA analysis. Uneventful vaginal delivery occurred at term following prophylactic platelet transfusion. Women of northwestern Puerto Rican descent with OCA should be offered testing for HPS. Identification of affected individuals may permit optimal obstetric management.