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The ever-shifting landscape of cataloging standards over the last decade has kept library and information science (LIS) educators on their toes, and continuing developments only promise to maintain this trend. Examples include the publication of the International Federation of Library Association & Institution’s (IFLA’s) conceptual model Library Reference Model (LRM) in 2017, the release of the new and heavily revised version of the cataloging content standard Resource Description and Access (RDA) in 2020, and Library of Congress’ upcoming Bibliographic Framework (BIBFRAME) standard for encoding and publishing library data. These new standards have altered the way in which cataloging work is conceived and discussed, radically changed the interfaces used for accessing cataloging documentation, and are now spurring the creation of new software and tools for cataloging work, including Library of Congress’ new Marva metadata editor. At the same time, the increasing inclusion of linked data projects in libraries, archives, and other cultural heritage institutions are requiring new skills, practices, and workflows that cataloging and metadata librarians must be prepared for. With many of these standards and initiatives not fully implemented in the majority of libraries, cataloging educators face a dilemma in deciding how best to prepare their students to successfully navigate this time of change, where old and new standards and practices intersect. The Technical Services Education SIG session will include a panel of three educators (two of whom are current cataloging practitioners) with unique perspectives on strategies for teaching toward emerging cataloging standards. After brief presentations by each of the panelists, audience members will be encouraged to ask questions and offer their own experiences and ideas concerning this area of LIS education. This conversation aligns well with the ALISE conference theme of “Go Back and Get It: From One Narrative to Many” as cataloging practice and education must be in constant dialogue about the preparation of LIS students for the lifespan of their careers. How can LIS educators prepare students for an environment in which different institutions are facing drastically different plans and timelines for the implementation of new standards? How can teaching practices be adjusted to best leverage current best practices alongside new strategies? And how can study of past, present, and emerging cataloging standards and practices provide a solid foundation on which LIS students can build throughout their careers? This panel will offer opportunities for LIS educators to reach back to knowledge and experiences concerning previous standards transitions, share best practices for addressing the current, dynamic environment, and look toward the future of cataloging and metadata education and preparation.

An idea was born at the 2019 Technical Services Education Special Interest Group session of the Association for Library and Information Science Education (ALISE) annual conference. Presenters and a...

Catalogers often need to make ethical decisions about their daily work. What is the starting point for defining cataloging ethics and how do practitioners define the concept? In this paper, the aut...

A comprehensive pain assessment is the first step in safe, effective pain management. Few studies have explored variations of strategies and measures for multidimensional pain assessment education in both verbal and nonverbal patients. In this retrospective cohort study, interprofessional health care students enrolled in a palliative care curriculum completed a pain assessment training, which taught the PQRSTA ("palliating factors, precipitating factors, previous treatments, quality, region, radiation, severity, temporal factors and associated symptoms") mnemonic as a strategy for assessing pain in verbal patients and the Pain Assessment in Advance Dementia and Checklist of Nonverbal Pain Indicators measures for nonverbal patients. The purpose of this study was to compare the change in attitudes, self-perceived skills, and knowledge regarding pain assessment before and after the training. Attitudes and self-perceived skills were assessed in the pretraining and posttraining survey, which was analyzed using χ2 test or Fisher exact test. Students' knowledge responses were analyzed using Wilcoxon signed rank test to assess accuracy of responses compared with the expert defined score. One hundred eighty-two students were included. Results showed a statistically significant improvement in attitudes related to applicability of pain measures and self-perceived skills. Overall, data did not support an increase in knowledge using the PQRSTA mnemonic, or Pain Assessment in Advance Dementia and Checklist of Nonverbal Pain Indicators measures. Future pain trainings should consider training on only 1 nonverbal pain measure, incorporating bedside assessments, and integrating real-time feedback.

Definitions of “quality cataloging” may differ from cataloger to cataloger and from institution to institution. If an objective definition of quality is elusive, how can an institution assess the quality of cataloging work? This article discusses definitions of quality cataloging in the literature and different ways it has been evaluated and measured. Academic library catalogers' perceptions of quality cataloging will also be explored, as well as how these perceptions are formed. The article concludes by suggesting ways cataloging departments can approach the creation and evaluation of quality cataloging in an ethical manner.

Palliative care patients who have pain are often unable to self-report their pain placing them at increased risk for under-recognized and under-treated pain. Use of appropriate pain assessment tools significantly enhances the likelihood of effective pain management and improved pain-related outcomes. This paper reviews selected tools and provides palliative care clinicians with a practical approach to selecting a pain assessment tool for non-communicative adult patients.

Well-designed, rigorously implemented instrumentation studies are essential to develop valid, reliable pain assessment tools in non-communicative (non-self-reporting) palliative care patients. When conducting a pain instrumentation study, a research team identified methodologic challenges surrounding informed consent, eligibility criteria, acute pain operational definitions, patient recruitment, missing data, and study-related training during a run-in phase at the beginning of the project and during the conduct of the study. The team dealt with these challenges through identifying root causes, implementing remedial measures, and collecting data to demonstrate improvement or resolution. Effective strategies included obtaining Institutional Review Board (IRB) approval for a waiver of informed consent, modifying eligibility criteria, ensuring that operational definitions and study procedures were consistent with clinical practice, decreasing time from screening to data collection to improve recruitment, increasing study nurse staffing by re-budgeting grant funds, focusing time and resources on high accruing clinical units, revising processes to minimize missing data, and developing detailed training for users of the instrument. With these multi-pronged solutions, the team exceeded the patient accrual target by 25% within the funding period and reduced missing data. While pain instrumentation studies in non-communicative patients have similar challenges to other palliative care studies, some of the solutions may be unique and several are applicable to other palliative care studies, particularly instrumentation research. The team's experience may also be useful for funders and IRBs.

Originality/Value – This chapter was written by four cataloging educators, who have extensive cataloging knowledge and experience and who have seen firsthand the benefits of cataloging education for all LIS students. As library professionals adapt, and given the increasing focus on users and their needs, the relevance and necessity of a robust understanding of cataloging and metadata creation principles is key going forward.

False memoirs are, in essence, autobiographical works that are presented initially as nonfiction, but are proven to be entirely or partially fabricated. These works are described as nonfiction when they are cataloged initially, but when the controversy surrounding them comes to light, there is uncertainty about what, if anything, to do about the contents of the bibliographic record if the work is retained in the collection. This study examines the practical concerns of cataloging false memoirs, such as changing the class number, modifying subject headings, and adding notes, as well as the ethical implications of these actions.

For the past 35 years, members of the Maxwell family have guided cataloging students and practitioners through the often labyrinthine standards of library cataloging practice. Margaret F. Maxwell w...

Patients receiving high-dose cytarabine as part of their chemotherapy regimen have a chance of experiencing neurotoxicities. Prompt identification of signs and symptoms can greatly reduce the chance of patients sustaining permanent neurologic damage. This article describes the development and successful implementation of an evidence-based, standardized neurologic assessment and documentation tool that was evaluated using a clinical utility questionnaire and an adherence audit.

Background aims Despite widespread use of umbilical cord blood (UCB) transplantation and distinct practice preferences displayed by individual UCB banks and transplant centers, little information exists on how processing variations affect patient outcomes. Methods We reviewed 133 adult double UCB transplants performed at a single center: 98 after reduced-intensity and 35 after myeloablative conditioning. Processing associated with contributing UCB banks and units was surveyed to identify differences in practice. We analyzed effect of selected variables on clinical outcomes of engraftment, dominance, transplant-related mortality, and survival. Results Eighty-eight percent of banks queried currently practice red blood cell (RBC) depletion before cryopreservation. This reflects a shift in practice because previously 65% of banks employed RBC-replete processing methods (i.e., cryopreservation or plasma/volume reduction). Neither neutrophil nor platelet engraftment was affected by processing conditions analyzed. RBC depletion was not associated with clinical outcomes, except in 17 recipients of 2 RBC-replete units, where survival was better than that observed in 116 recipients of ≥1 RBC-depleted units (hazard ratio 3.26, P = 0.004). When analyzed by attributes of the dominant unit, RBC depletion, time in storage, bank years in existence, and inventory size did not affect clinical outcomes. Postthaw viability and CD34 dose were factors impacting engraftment. Notably, all RBC-replete units in this cohort were washed in dextran-human serum albumin before infusion. Discussion These findings support continued utilization of the entire existing pool of cord blood units, despite recent trends in processing, and have important implications for banking resources and UCB selection practices.

In 2015 the Association for Library Collections and Technical Services Cataloging and Metadata Management Section (ALCTS CaMMS) Competencies for a Career in Cataloging Interest Group (CECCIG) charged a task force to create a core competencies document for catalogers. The process leading to the final document, the Core Competencies for Cataloging and Metadata Professional Librarians, involved researching the use of competencies documents, envisioning an accessible final product, and engaging in collaborative writing. Additionally, the task force took certain measures to solicit and incorporate feedback from the cataloging community throughout the entire process. The Competencies document was approved by the ALCTS Board of Directors in January 2017. Task force members who were involved in the final stages of the document’s creation detail their processes and purposes in this paper and provide recommendations for groups approaching similar tasks.

L’homme de Saint-Petersbourg au Siam : A.E. Olarovskij et la Mission de la Russie en Asie, 1898-1905Pendant les annees 1890, par suite de l’expansion des interets de la Russie imperiale en Chine et de son commerce maritime en Extreme-Orient, des consuls russes furent nommes dans les ports les plus importants de l’Asie du Sud-Est. Leur mission premiere consistait a proteger les interets commerciaux et maritimes de la Russie tout en entretenant des relations diplomatiques avec les puissances coloniales en place. Selon les periodes, ils furent charges de prospecter la region pour rechercher tant des zones de stockage du charbon pour approvisionner les navires que de nouveaux marches et d’observer de pres les dirigeants coloniaux. Mais en aucune facon ils ne devaient se meler des affaires de ces derniers ! Il ne s’est produit qu’une seule exception a cette regle, quand A.E. Olarovskij fut nomme ministre resident au Siam par le gouvernement russe. L’histoire des activites de ce diplomate dans le role croissant de la Russie en Asie du Sud-Est constitue l’un des episodes les plus interessants de l’histoire des consuls de la region et nous fournit une nouvelle approche des reves tsaristes pour la mission de la Russie en Asie au tournant du siecle, a savoir l’extension des ambitions imperiales en Asie du Sud-Est et en Chine et l’etablissement de relations avec l’Empire colonial francais en Indochine.

We report nine novel DNA alterations in the RET proto-oncogene in 12 unrelated cases identified by DNA sequencing of exons 10 and 11 of the gene. The novel variants K666E, IVS9-11G--A, D631V in cis with H665Q, D631E (with C634Y), E623K (in trans with C618S), 616delGAG (in trans with C609Y), Y606C, C630R, and R635-T636insELCR;T636P were detected in patients with various clinical presentations ranging from thyroid goiter, medullary thyroid carcinoma, and pheochromocytoma to classic multiple endocrine neoplasia type 2A. When novel DNA alterations are found, extended family studies can be helpful in determining the clinical significance of such findings. Segregation within families suggests that K666E and T636insELCR;T636P are likely to be disease-causing mutations. However, the mechanism by which they affect the normal activity of the RET receptor is unclear. Absence of segregation with disease was observed for E623K and 616delGAG. For the remainder of the DNA alterations, family studies were not possible, and the clinical significance of these novel variants needs further assessment. Additional case reports, animal models, and/or functional studies are needed to determine the clinical significance of these newly identified variants.

The diagnosis of Duchenne muscular dystrophy (DMD) has historically utilized either PCR or requires Southern blot analysis, a southern blot analysis, however, is not amenable to incorporation in a microdevice format. A PCR amplification-based method has been developed, and we have previously coupled this amplification with microchip separation of the PCR fragments for DMD diagnosis. Diagnoses of affected patients were performed by comparing exon concentrations to those of control samples amplified at the same time. To accurately identify mutations in patient samples, this work established normal ranges for the concentration of each amplified exon fragment using control samples amplified over successive days. Our studies show that the number of cycles used in the amplification process affects this range. Affected patient samples were analyzed using these normal ranges and the mutations detected by Southern blot analysis were also diagnosed using the microchip separation method. Employing the microchip separation method decreases the time required for the analysis, but the time required for DNA purification and PCR amplification must also be decreased for faster total analysis of patient samples. Development of microchip methods for these processing steps is one approach for reducing the individual times, while also providing the possibility of integrating these steps in a single device. Here we report on the microchip extraction of genomic DNA from whole blood using a novel sol–gel matrix that is easily formed in microdevices. IR-mediated PCR amplification of a β-globin fragment from genomic DNA followed by electrophoretic analysis on a single integrated microdevice is presented for the first time. Work towards the development of a micro-total analysis device for DMD diagnosis, through integration of all processing steps on a single device, is also discussed.

Positive control materials for clinical molecular genetic testing applications are currently in critically short supply or non-existent for many genetically based diseases of public health importance. Here we demonstrate that anonymous, residual, clinical blood samples are potential sources of viable lymphocytes for establishing Epstein-Barr virus (EBV)-transformed blood lymphocyte cell lines. We attempted to transform 34 residual blood samples, and analyzed transformation success with respect to sample age, anticoagulant, storage temperature, volume, hemolysis, and patient age and sex. In univariate analysis, sample age was significantly associated with transformation success (P = 0.002). The success rate was 67% (6 of 9) for samples 1 to 7 days old, 38% (3 of 8) for samples 8 to 14 days old and 0% for samples 15 to 21 (0 of 11) days old. When we controlled for sample age in multivariate logistic regression, anticoagulant and storage temperature approached significance (P = 0.070 and 0.087, respectively; samples in acid citrate dextrose (ACD) and refrigerated samples were more likely to transform). Based on these findings, we suggest that samples collected in either ACD or ethylene diamine tetraacetic acid, and up to 14 days old (refrigerated) or 7 days old (stored ambient), are reasonable candidates for EBV transformation. The transformation rate for samples that met these criteria was 63% (10 of 16). Implementation of this process could help alleviate the shortage of positive control materials for clinical molecular genetic testing.

The two known complementation groups of Niemann-Pick Type C disease, NPC1 and NPC2, result from non-allelic protein defects. Both the NPC1 and NPC2 (HE1) gene products are intimately involved in cholesterol and glycolipid trafficking and/or transport. We describe mutation analysis on samples from 143 unrelated affected NPC patients using conformation sensitive gel electrophoresis and DNA sequencing as the primary mutation screening methods for NPC1 and NPC2, respectively. These methods are robust, sensitive, and do not require any specialized laboratory equipment. Analyses identified two NPC1 mutations for 115 (80.4%) patients, one NPC1 mutation for 10 (7.0%) patients, two NPC2 mutations for five (3.5%) patients, one NPC2 mutation for one (0.7%) patient, and no mutations for 12 (8.4%) patients. Thus, mutations were identified on 251 of 286 (88%) disease alleles, including 121 different mutations (114 in NPC1 and seven in NPC2), 58 of which are previously unreported. The most common NPC1 mutation, I1061T, was detected on 18% of NPC alleles. Other NPC1 mutations were mostly private, missense mutations located throughout the gene with clustering in the cysteine-rich luminal domain. Correlation with biochemical data suggests classification of several mutations as severe and others as moderate or variable. The region between amino acids 1038 and 1253, which shares 35% identity with Patched 1, appears to be a hot spot for mutations. Additionally, a high percentage of mutations were located at amino acids identical to the NPC1 homolog, NPC1L1. Biochemical complementation analysis of cases negative for mutations revealed a high percentage of equivocal results where the complementation group appeared to be non-NPC1 and non-NPC2. This raises the possibilities of an additional NPC complementation group(s) or non-specificity of the biochemical testing for NPC. These caveats must be considered when offering mutation testing as a clinical service. Hum Mutat 22:313–325, 2003. © 2003 Wiley-Liss, Inc.

This is the first description of slowly progressive Niemann-Pick disease type C (NPC) without the typical lysosomal storage in bone marrow and viscera in two descendants of a group of 17th century French-Canadians. The index patient was a married 43-year-old woman with onset of dementia in her thirties, later followed by the development of ataxia and athetoid movements. Her autopsy disclosed frontal lobe atrophy, neurolysosomal storage with oligolamellar inclusion and tau-positive neurofibrillary tangles. Of the 119 family members screened, only a married 42-year-old sister displayed symptoms of a dementia. Both women displayed vertical supranuclear ophthalmoplegia; expressive aphasia; concrete, stimulus-bound, perseverative behavior; and impaired conceptualization and planning. Cultured fibroblasts showed decreased cholesterol esterification and positive filipin staining, but no mutation was detected in coding or promoter regions of the NPC1 gene using conformation sensitive gel electrophoresis and sequencing. Sequencing showed a homozygous gene mutation that is predicted to result in an amino acid substitution, V39M, in the cholesterol binding protein HE1 (NPC2). Adult-onset NPC2 with lysosomal storage virtually restricted to neurons represents a novel phenotypic and genotypic variant with diffuse cognitive impairment and focal frontal involvement described for the first time.

Preimplantation genetic diagnosis (PGD) is a procedure that allows embryos to be tested for genetic disorders before they enter the uterus and before pregnancy has begun. Embryos obtained by in vitro fertilization undergo a biopsy procedure in which one or two cells are removed and tested for a specific disorder. If the cell is unaffected, the embryo from which it was taken is judged to be free of the disorder. The embryo can then be transferred to the uterus to initiate pregnancy. Couples whose children are at increased risk for a specific genetic disorder can benefit from PGD. Some of these couples may have affected family members or family ancestry that puts them at high risk for transmitting a particular disorder to their offspring. PGD is an alternative to prenatal tests such as amniocentesis or chorionic villus sampling and since it is performed before a pregnancy has begun, it may be more acceptable to couples who have either had an affected child, previous termination of pregnancy, or who have objections to termination of pregnancy. PGD tests have largely focused on two methodologies: fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). This review will focus on the use of PCR-based methodologies to diagnose single gene disorders in single cells; specifically describing the characteristics and limitations of single cell PCR and mutation detection strategies which have been developed for use in clinical PGD. The hundreds of cycles of preimplantation diagnosis performed to date have resulted in the birth of several hundred healthy children. 1 As shown in Table 1​1 , the genetic conditions for which PGD has been applied are numerous and the various methods used for diagnosis reflect the heterogeneity of causative mutations. Table 1. Strategies for PCR-Based Tests Used for Clinical Preimplantation Genetic Diagnosis The first clinical application of PGD used a generic PCR protocol for gender determination to avoid the transfer of male embryos which have a 50% probability of being affected by an X-linked recessive disorder. Gender was determined in a single blastomere by a single round of PCR using primers for Y-chromosome specific repetitive DNA sequences. The presence of Y-specific PCR amplification products was indicative of a male embryo and the absence of products was scored as female. 2 Although this approach had some success, a misdiagnosis, presumably due to amplification failure, did occur and emphasized the challenges inherent in single cell analysis and, more specifically, the danger in relying on the absence of amplification to diagnose genotype. 3 Subsequently, PCR protocols for preimplantation gender determination were refined to include primer sets which simultaneously amplify sequences common to both sex chromosomes (for example single copy genes such as ZFX/ZFY, 4 AMELX/AMELY, 5 ) and repetitive sequences such as DXZ1 and DYZ1. 6, 7 Sequences common to the sex chromosomes are identical at the site of primer annealing but differ internally in terms of size or include minor polymorphisms. Despite these technical improvements, the majority of embryo sexing is now accomplished using fluorescent in situ hybridization (FISH) which is less prone to contamination and can also provide the copy number for each chromosome tested thereby potentially avoiding the transfer of common chromosome abnormalities such as triploidy or X-monosomy. 8, 9 Although FISH has largely superseded PCR for sex determination, the specific diagnosis of single-gene defects remains dependent on DNA amplification with PCR. In the case of X-linked disorders, testing of the specific gene has the added advantage of ensuring that all embryos free of the mutant gene can be selected for transfer, irrespective of gender. 10, 11, 12 The list of disorders and the particular mutation detection strategies used for PCR-based clinical PGD application are given in Table 1​1 .

Duchenne muscular dystrophy (DMD), a genetic disease caused by mutations in the X chromosome, is currently diagnosed by Southern blot analysis. Affected males and female carriers are identified by the detection of duplicated or deleted exons in the dystropin gene. Disadvantages of this method include the large number of fragments required for hybridization to determine genomic alterations and the time-consuming, expensive, and tedious nature of the analysis. The deletions/duplications seen in DMD tend to be located at certain “hot spot” regions of the gene, however, allowing easy detection of a great number of cases by interrogating a limited number of PCR-amplified DNA fragments. Chamberlain and coworkers (1)(2) developed primers to amplify nine fragments from known deletion sites in a single multiplex PCR amplification. Beggs et al. (3) defined additional primers that amplify nine fragments in a second multiplex PCR. This total set of 18 fragments allows >97% of the deletions detectable by Southern blot analysis to be detected rapidly and accurately by PCR. Analysis of the PCR fragments is most frequently carried out on slab gels, but both the presence and amount of the correctly sized fragments are important because carriers have both the mutated and wild-type gene. Many clinical laboratories that offer DMD testing do not provide carrier testing because of the technical difficulties associated with quantitative analysis. To speed analysis and automate quantification, several groups have exploited capillary electrophoresis (CE) for the separation of DMD-relevant fragments (4)(5)(6). One of the groups that reported DMD detection by CE transferred their method to an electrophoretic microdevice (6), a very rapid separation technique demonstrated to be an effective tool for use in clinical analyses (7)(8)(9)(10)(11)(12)(13). Although these reports show CE and microchip electrophoresis …

We report preliminary data for three previously unrecognized hemoglobin (Hb) variants due to mutations of the α1-globin gene, that were initially ascertained by either chromatographic, electrophore...

Background aims Quality cell manufacturing processes require a clean laboratory environment. Methods This report was aimed at describing current cleaning and sanitization practices reported by facilities that manufacture many types of cellular therapy products for clinical use. It is our hope that this report may provide the groundwork for guidance recommendations directed at developing consensus standards for cleaning and sanitization practices across the globe. Facility sanitization is a central issue to regulatory and accreditation bodies. Facilities are required to develop plans to assess sanitization practices and test cleaning effectiveness. Results This document provides information on how this is performed in different facilities and may allow newer, smaller or less developed facilities to build, enhance or revise their current quality program by using experience and expertise in facility sanitization reported herein. Conclusions This report summarizes the results of the latest survey and compares results with those previously reported. New and relevant trends in the field provide important information and will provide important information for establishing guidelines.

Niemann-Pick disease type C (NPC) is a fatal, autosomal recessive lipidosis characterized by lysosomal accumulation of unesterified cholesterol and multiple neurological symptoms, such as vertical supranuclear ophthalmoplegia, progressive ataxia, and dementia. More than 90% of cases of NPC are due to a defect in Niemann-Pick C1 (NPC1), a late endosomal, integral membrane protein that plays a role in cholesterol transport or homeostasis. Biochemical diagnosis of NPC has relied on the use of patient skin fibroblasts in an assay to demonstrate delayed low-density lipoprotein (LDL)-derived cholesterol esterification and a cytological technique-filipin staining-to demonstrate the intracellular accumulation of cholesterol. A small percentage of patients, referred to as "NPC variants," present with clinical symptoms of NPC but show near-normal results of these biochemical tests, making laboratory confirmation of NPC disease problematic. Here, we demonstrate that NPC-variant fibroblast samples can be detected as sphingolipid storage disease cells, using a fluorescent sphingolipid analog, BODIPY-lactosylceramide. This lipid accumulated in endosomes/lysosomes in variant cells preincubated with LDL cholesterol but targeted to the Golgi complex in normal cells under these conditions. The reproducibility of this technique was validated in a blinded study. In addition, we performed mutation analysis of the NPC1 gene in NPC variant and "classical" NPC cell samples and found a high incidence of specific mutations within the cysteine-rich region of NPC1 in variants. We also found that 5 of the 12 variant cell samples had no apparent defect in NPC1 but were otherwise indistinguishable from other variant cells. This is a surprising result, since, in general, approximately 90% of patients with NPC possess defects in NPC1. Our findings should be useful for the detection of NPC variants and also may provide significant new insight regarding NPC1 genotype/phenotype correlations.

A 55-bp deletion in exon 9 of the glucocerebrosidase gene was identified in a 28-year-old male affected with Gaucher disease. The diagnosis was established during an evaluation for mild pancytopenia and was confirmed by bone marrow histology and biochemical studies. The patient is of German ancestry. Initial DNA testing indicated homozygosity for the N370S mutation. However, subsequent testing of the patient's parents suggested that the patient and his mother carried a null allele by our assay for N370S. Further molecular studies identified a 55-bp deletion in exon 9 of the glucocerebrosidase gene (g.6767_6822del55). This deletion has been previously reported in a patient with severe Gaucher disease (1), and is present in the glucocerebrosidase pseudogene. In the previously reported case, initial DNA testing also suggested the genotype N370S/N370S, but further mutation studies were undertaken because clinical severity was greater than expected for that genotype. In contrast, our patient has an unusually mild clinical course. Thus, clinical severity cannot be reliably used to determine when to test for the presence of the 55-bp deletion. While the 55-bp deletion is not reported to be common, its actual frequency may be underestimated since it eludes detection by many standard clinical assays for Gaucher disease. This report points out the need to consider this deletion mutation which may cause erroneous interpretation of results in existing assays for the common mutations N370S and L444P. Furthermore, the importance of recommending parental analysis for individuals who test homozygous for autosomal mutations is highlighted.

Twenty percent of colorectal cancers (CRCs) arise in people who have a family history of CRC in at least one other relative. Although a fraction of these CRCs are explained by two well-described autosomal dominant syndromes-5% by hereditary nonpolyposis colorectal cancer (HNPCC) and 1% by familial adenomatous polyposis (FAP)-the cause of the remaining 14% of familial aggregates of CRC is unknown. Many cases of HNPCC are due to germline mutations in DNA mismatch repair genes, leading to the tumor phenotype of microsatellite instability (MSI), and most cases of FAP are caused by germline APC mutations. To date, non-FAP familial CRC aggregates have not been evaluated for germline APC mutations. In this study, we examined the involvement of germline APC mutations in 79 individuals with CRC who had early-age onset of their cancer (age G (proline --> proline) in exon 4 was observed. Additionally, four intervening sequence (IVS) alterations were detected: IVS2-53t-->c in 3 cases; IVS4-17ins T in 3 cases; IVS5+32t-->c in 16 cases; and IVS5+33g-->a in 1 case. All appeared to be polymorphisms present in similar proportions in an average-risk population. We conclude that germline APC mutations do not account for familial MSS (stable microsatellite) CRC associated with few synchronous polyps.

We report a novel mutation at alpha66(E15)Leu-->Pro (alpha2) (CTG-->CCG), that we have named Hb Dartmouth for the medical center at which the patients were cared for, in monozygotic twins who also inherited the Southeast Asian alpha-thalassemia-1 deletion. The mother, of Khmer ancestry, is heterozygous for alpha-thalassemia-1. The father, who is of Scottish-Irish ancestry, is a silent carrier of the codon 66 mutation. The twins had severe neonatal anemia requiring transfusion.

Purpose: The phenotype correlations for interstitial duplications that include the Prader-Willi/Angelman syndrome critical region are not well established. We describe two such duplication cases, one of which was of maternal origin and the other was paternal. Methods: High resolution G-banding, fluorescence in situ hybridization (FISH) for SNRP-N and D15S10 were used for cytogenetic analysis. Southern blot analyses based on parent of origin specific DNA methylation at D15S63 (PW71) locus were utilized for detection of methylated and unmethylated fragments. Results: The duplication was established by the FISH analysis. The molecular pattern suggested a maternal origin of the duplication in patient 1 and a paternal origin in patient 2. Patient 1 (2 years old) had developmental and speech delays with pervasive developmental disorder or mild autism, strabismus, and normal growth parameters with seizures. Patient 2 (16 years old) had global developmental delay, verbal IQ of 94, depression, obesity, food-seeking behavior, and significant behavioral problems that included self-injurious tendencies. Neither patient had significant dysmorphic features or abnormalities of internal organs. Conclusion: The two cases suggest that some patients with 15g11.2g12 duplication may have significant anomalies, and there appear to be phenotypic differences between maternal and paternal transmission of the duplication.

More than 900 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been reported to the cystic fibrosis (CF) consortium. A missense mutation, S1235R, was originally reported in a CF patient with a second mutation (G628R) on the same chromosome. The clinical significance of S1235R was not clear. S1235R is not among the commonly reported mutations, and it is not routinely screened for in most laboratories. However, we have detected the S1235R allele at a frequency that is significantly higher than that of many other CF mutations. Among more than 3,000 patients tested for either a possible diagnosis of CF or to determine CF carrier status, we identified 51 patients heterozygous for S1235R. No patients were homozygous for S1235R. Five patients were compound heterozygotes for a second CFTR mutation: two cases (one family) were N1303K/S1235R and three unrelated cases were ΔF508/S1235R. Our data suggest that S1235R, when combined with a second CF mutation, may be pathogenic, although phenotypic manifestations appear to be variable. The possibility that this represents a rare polymorphism cannot be discounted completely. Genetic counseling is difficult when S1235R is identified, even in the presence of a second known mutation, especially in prenatal cases. Am. J. Med. Genet. 95:361–365, 2000. © 2000 Wiley-Liss, Inc.

Background: Current methods for molecular-based diagnosis of disease rely heavily on modern molecular biology techniques for interrogating the genome for aberrant DNA sequences. These techniques typically include amplification of the target DNA sequences followed by separation of the amplified fragments by slab gel electrophoresis. As a result of the labor-intensive, time-consuming nature of slab gel electrophoresis, alternative electrophoretic formats have been developed in the form of capillary electrophoresis and, more recently, multichannel microchip electrophoresis. Methods: Capillary electrophoresis was explored as an alternative to slab gel electrophoresis for the analysis of PCR-amplified products indicative of T- and B-cell malignancies as a means of defining the elements for silica microchip-based diagnosis. Capillary-based separations were replicated on electrophoretic microchips. Results: The microchip-based electrophoretic separation effectively resolved PCR-amplified fragments from the variable region of the T-cell receptor-γ gene (150–250 bp range) and the immunoglobulin heavy chain gene (80–140 bp range), yielding diagnostically relevant information regarding the presence of clonal DNA populations. Although hydroxyethylcellulose provided adequate separation power, the need for a coated microchannel for effective resolution necessitated additional preparative steps. In addition, preliminary data are shown indicating that polyvinylpyrrolidone may provide an adequate matrix without the need for microchannel coating. Conclusions: Separation of B- and T-cell gene rearrangement PCR products on microchips provides diagnostic information in dramatically reduced time (160 s vs 2.5 h) with no loss of diagnostic capacity when compared with current methodologies. As illustrated, this technology and methodology holds great potential for extrapolation to the abundance of similar molecular biology-based techniques.

Autosomal dominant cerebellar ataxias are a heterogeneous group of neurodegenerative disorders that generally present in adulthood. Spinocerebellar ataxia type 2 typically presents with progressive cerebellar symptoms, slow ocular saccades, and peripheral neuropathy. The onset of symptoms is usually between 20 and 40 years. We describe an infant who presented with neonatal hypotonia, developmental delay, and dysphagia. Ocular findings of retinitis pigmentosa were noted at 10 months. Her father had mild spinocerebellar ataxia first noted at age 22 years. Molecular studies of the SCA2 gene showed a CAG expansion of 43 repeats in the father and an extreme CAG repeat expansion of more than 200 in the baby. Our report expands the known phenotype and genotype of SCA2. Testing for dominant ataxias should be included in the evaluation of infants with nonspecific progressive neurologic symptoms and retinitis pigmentosa, especially in cases with a positive family history for spinocerebellar ataxia.