Subject(s)
Clinical Laboratory Information Systems/statistics & numerical data , Internet/statistics & numerical data , Attitude to Computers , Computer Communication Networks/statistics & numerical data , Educational Status , Hospital Administrators/statistics & numerical data , Physician Executives/statistics & numerical data , Surveys and Questionnaires , United StatesABSTRACT
While a recent survey shows that more laboratorians approve of CLIA now than in the past, a considerable enclave remain opposed to this law. Among the key issues that continue to dishearten and incite the clinical lab: the proposed exemption of POLs and diminished personnel standards.
Subject(s)
Laboratories/standards , Quality Assurance, Health Care/legislation & jurisprudence , Attitude of Health Personnel , Certification , Data Collection , Efficiency, Organizational , Facility Regulation and Control/legislation & jurisprudence , Guideline Adherence , Laboratories/legislation & jurisprudence , Medical Laboratory Personnel/psychology , Medical Laboratory Personnel/statistics & numerical data , Physicians' Offices , Professional Competence , United StatesSubject(s)
Laboratories/standards , Quality Assurance, Health Care/statistics & numerical data , Accreditation , Attitude of Health Personnel , Clinical Competence , Data Collection , Documentation , Facility Regulation and Control , Humans , Laboratories/statistics & numerical data , Quality Assurance, Health Care/methods , Self-Evaluation Programs , United StatesABSTRACT
Chondrodysplasia punctata (CP) is a heterogeneous group of bone dysplasias that are characterized by abnormal calcium deposition in areas of enchondral bone formation. The existence of an X-linked recessive form of chondrodysplasia punctata (CDPX) has been recognized in patients who are nullisomic for the Xp22.3 region, presenting with complex phenotypes. The gene of CDPX has been identified recently, and five point mutations of the gene, named ARSE, have been described. Here, we report on the clinical and molecular characterization of a patient with CDPX. The patient presented at birth with cranial and facial anomalies and short stature; an x-ray skeletal survey showed punctate calcifications and striking hand and foot abnormalities. Single strand conformation polymorphism (SSCP) and sequence analysis of the patient's DNA allowed the identification of a new mutation of the ARSE gene; this mutation causes an amino acid substitution from cysteine to tyrosine at position 492 of the ARSE predicted protein product. The clinical description of patients with CDPX due to known mutation of the ARSE is of interest for the precise delineation of the clinical spectrum of the disease.
Subject(s)
Arylsulfatases/genetics , Chondrodysplasia Punctata/genetics , Point Mutation/genetics , Chondrodysplasia Punctata/diagnostic imaging , DNA Mutational Analysis , Genetic Linkage , Humans , Infant, Newborn , Male , Polymorphism, Single-Stranded Conformational , Radiography , X Chromosome/geneticsABSTRACT
CDG syndrome (CDGS) type I is the most frequent form of a group of metabolic disorders characterised by a defect of the carbohydrate moiety of glycoproteins. A large number of plasma glycoproteins, including clotting factors and inhibitors, are decreased and stroke-like episodes have been described in about half of the reported patients. We studied blood coagulation factors, inhibitors and D-dimer plasma levels in four subjects, aged 12-23 years, with CDGS type I. Factors VIII, XI, antithrombin III activity, antigen plasma levels of antithrombin III, free protein S and protein C were decreased whereas protein C as activity was normal. In addition two patients had reduction of factors II, V, VII, IX, X reflecting the phenotypic heterogeneity associated with CDGS type I. D-dimer plasma concentrations were elevated in all subjects. The hypercoagulable state as consequence of the combined deficiencies of coagulation inhibitors could contribute to the stroke-like phenomena in CDGS type I.
Subject(s)
Blood Coagulation Factors/physiology , Congenital Disorders of Glycosylation/blood , Adolescent , Adult , Blood Coagulation Factors/antagonists & inhibitors , Child , Female , Hemostasis , Humans , Male , Partial Thromboplastin Time , Prothrombin TimeABSTRACT
The carbohydrate-deficient glycoprotein (CDG) syndromes are a group of genetic multisystem disorders with invariable involvement of the nervous system including severe olivopontocerebellar atrophy. We report two sets of sibs in whom the diagnosis of CDG syndrome type 1 was recognized at an older age because of marked olivopontocerebellar atrophy seen on MRI. Previous CT findings were interpreted as showing Dandy-Walker malformation. Three of the patients are also among the oldest reported with this syndrome.
Subject(s)
Congenital Disorders of Glycosylation/complications , Olivopontocerebellar Atrophies/complications , Adult , Brain/pathology , Child , Congenital Disorders of Glycosylation/diagnosis , Female , Humans , Italy , Magnetic Resonance Imaging , Male , Olivopontocerebellar Atrophies/diagnosisABSTRACT
Four patients with carbohydrate deficient glycoprotein (CDG) syndrome type I underwent ophthalmic examination. All of them had retinitis pigmentosa with extinguished scotopic electroretinogram. The importance of CDG syndromes as one of the metabolic causes of retinal dystrophy with 'bony spicule' pigment is stressed.
Subject(s)
Carbohydrates/deficiency , Glycoproteins/chemistry , Retinal Degeneration/etiology , Adolescent , Adult , Child , Evoked Potentials, Visual , Female , Humans , Male , Retinal Degeneration/genetics , Syndrome , Visual AcuityABSTRACT
The molecular defect responsible for a case of mild osteogenesis imperfecta (OI) with repeated femoral fractures was investigated. The proband and his mother, who presented minor OI signs but no bone fractures, were shown to produce normal and abnormal type-I procollagen molecules in their dermal fibroblasts. The molecular defect was localized in about half of the proband's pro alpha 1(I) mRNA molecules by chemical cleavage with piperidine of hydroxylamine-reacted mRNA:cDNA heteroduplexes. The corresponding region was reverse-transcribed and amplified by polymerase chain reaction (PCR). Cloning and sequencing of the amplified products revealed in both subjects a G-to-A transition in the first base of codon 901 of the alpha 1(I) triple helical domain, which led to a serine for glycine substitution. Allele-specific oligonucleotide hybridization to amplified genomic DNA from fibroblasts and leukocytes confirmed the heterozygous nature of both patients and proved the absence of mosaicism. The presence of the mutation was excluded in other healthy family members, who were reported to have bluish selerae. The mild phenotypic outcome of this newly characterized mutation contradicts previous findings on glycine substitutions in the C-terminal region of collagen triple helix, most of which caused lethal OI.
Subject(s)
Chromosome Aberrations , Collagen/genetics , Genes/genetics , Osteogenesis Imperfecta/genetics , Base Sequence , Child , Codon/genetics , DNA Mutational Analysis , Female , Gene Expression , Genes, Dominant , Genetic Variation , Glycine/genetics , Humans , Male , Middle Aged , Molecular Sequence Data , Mutation , Pedigree , Polymerase Chain Reaction , Procollagen/genetics , RNA, Messenger/genetics , Serine/geneticsABSTRACT
Autosomal dominant inheritance of a mild form of osteogenesis imperfecta (osteogenesis imperfecta type I) with different phenotypic expression was found in a family. Phenotypic expression was different for the affected mother and son, in the presence of the same biochemical results. Dermal fibroblast cultures synthesized normal and mutant type I collagen alpha chains. Collagen heterotrimers containing abnormal chains were overmodified along the entire triple helical domain and showed an unusually low denaturation temperature, so far found only in lethal cases. The mild phenotype in the family is probably due to the fact that abnormal type I collagen molecules are more likely to be degraded than utilized in the extracellular matrix.
Subject(s)
Body Temperature , Collagen/genetics , Osteogenesis Imperfecta/genetics , Cells, Cultured , Child, Preschool , Collagen/chemistry , Collagen/metabolism , Cyanogen Bromide , Female , Fibroblasts/metabolism , Humans , Macromolecular Substances , Male , Mutation , Osteogenesis Imperfecta/metabolism , Pedigree , Phenotype , Protein Conformation , Protein DenaturationABSTRACT
Five cases of Roberts syndrome (RS) in four nuclear families are reported and the wide range of phenotypic variation among them is described. This is in contrast with the remarkable uniformity of the cytogenetic findings. Indirect immunofluorescence with seric antibodies from patients with CREST, revealed that the centromeric structures are normal in RS thus confirming J. German's assumption that the chromatid repulsion is confined to the heterochromatin. The authors quantified the phenomenon of centromeric heterochromatin separation (as occasionally revealed by C-bands in normal subjects) in obligate heterozygotes and possible heterozygotes for RS. The results are indicative of the possibility to screen for heterozygotes. The nosology of RS and related syndromes is discussed in view of the cytogenetic findings and the natural history of the disease.
Subject(s)
Abnormalities, Multiple/genetics , Genetic Carrier Screening , Genetic Variation/genetics , Female , Humans , Karyotyping , Male , Pedigree , Phenotype , SyndromeABSTRACT
Clinical variability and causal heterogeneity of holoprosencephaly is discussed in relation to several newborn infants with cyclopia (cases 4,5,6), cebocephaly (cases 2,3), and premaxillary agenesis (case 1). In subjects with holoprosencephaly, the presence of multiple malformations is an indicator of concomitant chromosome aberrations, as in present case 1 (Down syndrome) and case 3 (trisomy 13). Cases 5 and 6 are two monozygotic twins with the same type of cyclopia and alobar holoprosencephaly recognized by prenatal ultrasonography. The diagnostic importance of ultrasonographic, cytogenetic, and pathological studies is pointed out in view of etiologic evaluation, genetic counseling, and prevention of holoprosencephaly.
Subject(s)
Chromosome Aberrations , Holoprosencephaly/genetics , Abnormalities, Multiple , Chromosomes, Human, Pair 13 , Down Syndrome/genetics , Face/abnormalities , Female , Head/abnormalities , Humans , Infant, Newborn , Male , TrisomyABSTRACT
The Authors report a case of a rare and very voluminous teratoma with uncommon location (the right cervico-facial region) and extracranial seat in a female newborn. The teratoma was excised in the 18th day of life. It showed cystic and solid lesions. The tissues were derived from the three germ layers and were prevalently mature; only a bit of them was represented by embryonic mesenchymal tissue. The baby, followed and checked up during all the first year of her life, showed a normal evolution and absence of recurrences.