Subject(s)
Child Development Disorders, Pervasive/genetics , Hemophilia A/genetics , Intellectual Disability/genetics , Language Development Disorders/genetics , Psychomotor Disorders/genetics , Child Development Disorders, Pervasive/diagnosis , Child, Preschool , Chromosome Duplication , Chromosomes, Human, X/genetics , Consanguinity , DNA Mutational Analysis , Factor VIII/genetics , Follow-Up Studies , Hemophilia A/diagnosis , Humans , Infant , Intellectual Disability/diagnosis , Language Development Disorders/diagnosis , Male , Mutation, Missense , Oligonucleotide Array Sequence Analysis , Pedigree , Psychomotor Disorders/diagnosis , Sex Chromosome AberrationsSubject(s)
Hemophilia A/complications , Hemophilia A/diagnosis , Hepatolenticular Degeneration/complications , Hepatolenticular Degeneration/diagnosis , Adenosine Triphosphatases/genetics , Cation Transport Proteins/genetics , Chromosome Deletion , Chromosome Inversion , Copper-Transporting ATPases , DNA Mutational Analysis , Early Diagnosis , Factor VIII/genetics , Factor VIII/therapeutic use , Genetic Carrier Screening , Hemophilia A/genetics , Hemophilia A/therapy , Hepatolenticular Degeneration/genetics , Hepatolenticular Degeneration/therapy , Humans , Introns , Liver Function Tests , Male , Penicillamine/therapeutic use , Ultrasonography , Vitamin B 6/therapeutic useSubject(s)
Anticoagulants/therapeutic use , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Down Syndrome/complications , Down Syndrome/diagnosis , Enoxaparin/therapeutic use , Renal Veins , Thrombophlebitis/diagnosis , Thrombophlebitis/drug therapy , Thrombosis/diagnosis , Thrombosis/drug therapy , Vena Cava, Inferior , Adolescent , Antibodies, Antiphospholipid/blood , Anticoagulants/adverse effects , Antithrombins/adverse effects , Antithrombins/therapeutic use , Diagnosis, Differential , Disease Progression , Dose-Response Relationship, Drug , Enoxaparin/adverse effects , Female , Hirudins/adverse effects , Humans , Immunoglobulin M/blood , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , beta 2-Glycoprotein I/immunologyABSTRACT
BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder causing oculocutaneous albinism, bleeding disorder and ceroid lipofuscinosis. Platelets from HPS patients are characterized by the absence of dense (delta)-bodies. There are eight known human HPS GENES (HPS1-HPS8), each leading to a particular clinical HPS subtype. Restrictive lung disease, granulomatous colitis and cardiomyopathy have been described in HPS1 patients. PATIENTS: We identified HPS1 in Russian and in German siblings. All four patients show a typical HPS phenotype. The two older Russian patients demonstrate excessive bleeding after tooth extractions, recurrent epistaxis and hematomas. The two younger German patients suffer only from hematomas, so far. METHODS/RESULTS: Patients' platelets showed severe pathological agglutination/aggregation. Flow cytometry analysis demonstrated absence of platelet delta-granule secretion. Three different mutations in the HPS1 gene were found in the two families. Two mutations, p.H119delC and p.Q397delC identified in the Russian siblings had been previously described. The German siblings presented with a novel frameshift mutation (p.Q32_S33delCAGT) and the known p.Q397delC mutation. CONCLUSION: Patients with oculocutaneous albinism should be investigated for increased clinical bleeding symptoms. In case of increased bleeding symptoms, analyses of primary hemostasis should be initiated to confirm HPS. Molecular genetic investigations should be performed to distinguish the different subtypes of HPS which is important for therapy and prognosis.
Subject(s)
DNA Mutational Analysis , Genetic Carrier Screening , Genotype , Hermanski-Pudlak Syndrome/genetics , Adult , Age of Onset , Alleles , Bleeding Time , Child , Child, Preschool , Chromosome Deletion , Codon, Nonsense/genetics , Exons , Female , Frameshift Mutation/genetics , Hermanski-Pudlak Syndrome/blood , Humans , Male , Pedigree , Phenotype , Platelet Function Tests , Sequence Analysis, DNA , Young AdultABSTRACT
The genotype-phenotype relationship of compound heterozygous protein S-deficiency in a 7-year-old girl with reduced protein S-levels and a severe cerebral sinovenous thrombosis is illustrated. In this patient we identified a novel deletion in the protein S-gene causing a compound heterozygous state and subsequently a symptomatic protein S-deficiency. In case of thrombosis analysis of protein S is recommended. Low levels of protein S should be further investigated by molecular diagnostics.
Subject(s)
DNA Mutational Analysis , Genetic Carrier Screening , Genotype , Phenotype , Protein S Deficiency/genetics , Sinus Thrombosis, Intracranial/genetics , Anticoagulants/therapeutic use , Cerebral Infarction/diagnosis , Cerebral Infarction/drug therapy , Cerebral Infarction/genetics , Child , Chromosome Deletion , Epilepsy, Generalized/drug therapy , Epilepsy, Generalized/etiology , Female , Follow-Up Studies , Humans , Intracranial Hypertension/diagnosis , Intracranial Hypertension/drug therapy , Intracranial Hypertension/genetics , Magnetic Resonance Angiography , Mutation, Missense/genetics , Protein S Deficiency/diagnosis , Protein S Deficiency/drug therapy , Sinus Thrombosis, Intracranial/diagnosis , Sinus Thrombosis, Intracranial/drug therapy , Thalamic Diseases/diagnosis , Thalamic Diseases/drug therapy , Thalamic Diseases/geneticsSubject(s)
Afibrinogenemia/pathology , Fingers/pathology , Hemarthrosis/pathology , Adolescent , Afibrinogenemia/complications , Disease Progression , Humans , Male , Necrosis , Young AdultSubject(s)
Femur , Hematoma/etiology , Hemophilia A/complications , Accidental Falls , Hematoma/diagnosis , Hemophilia A/pathology , Humans , Infant , Magnetic Resonance Imaging , MaleABSTRACT
The presence and role of septin proteins in yeast is well documented, but there is a growing appreciation for this family of proteins beyond yeast and extending to human cells. In this report we present the characterization and comparison of two highly similar human septin genes, PNUTL1 and PNUTL2. We compare the exon/intron structure of both genes, the steady-state mRNA levels in tumor cell lines and adult organs, the conceptual translation products from alternatively processed mRNAs and the development of specific immunologic reagents distinguishing either PNUTL1 or PNUTL2. The results illustrate a remarkable similarity between the two genes and their protein products while identifying specific differences in mRNA expression patterns. A summary of the described functional roles for mammalian septins is discussed along with an attempt to assimilate the alternative nomenclature existing for the same human septins, such as references to PNUTL1 and PNUTL2 as hCDCrel-1 and hCDCrel-2, respectively. The characterization of PNUTL1 and PNUTL2 represents a fundamental step in completing the characterization of the entire family of human septin genes.
