AUDITORÍA DE GESTIÓN DEL CONOCIMIENTO. RETROSPECTIVA Y CONSTRUCCIÓN DEL CONCEPTO

RESUMEN El conocimiento representa un activo intangible y estratégico que genera ventajas competitivas en las organizaciones, de ahí la importancia de auditar su gestión. El objetivo del presente trabajo es construir una definición de auditoría de gestión del conocimiento (AGC) a partir del análisis crítico de 50 conceptos y las variables para el estudio de la AGC (adaptadas de Shahmoradi et al. (2015)). Se analiza la frecuencia de aparición de las variables en las definiciones, la relación de los autores con las variables definidas con el software UCINET 6.0. Se construye la definición de AGC con el uso de un mapa conceptual de AGC y el empleo del software Cmaps Tools, versión 5.03 Lite. PALABRAS CLAVE: auditoría de gestión del conocimiento, definiciones, variables. REFERENCIAS BIBLIOGRÁFICAS (estilo APA de citas) Alexandru, G. (2011). Above and beyond knowledge auditing. Sibiu Alma Mater University Journals, 4(2). Antonova, A., & Gourova, E. (2009). Business patterns for knowledge audit implementation within SMEs. http://ceur-ws.org/Vol-566/C2_KnowledgeAudit.pdf Burnet, S., Illingworth, L., & Webster, L. (2004). Knowledge Auditing and Mapping: A pragmatic Approach. Knowledge and Process Management, 11(1), 25-37. Dalkir, K. (2005). Knowledge Management in Theory and Practice. Oxford: Elsevier

Parental Mosaicism in PAX6 Causes Intra-Familial Variability: Implications for Genetic Counseling of Congenital Aniridia and Microphthalmia

Mutations in PAX6 are involved in several developmental eye disorders. These disorders have considerable phenotypic variability, ranging from panocular forms of congenital aniridia and microphthalmia to isolated anomalies of the anterior or posterior segment. Here, we describe 3 families with variable inter-generational ocular expression of aniridia, iris coloboma, or microphthalmia, and an unusual transmission of PAX6 mutations from an unaffected or mildly affected parent; all of which raised suspicion of gonosomal mosaicism. We first identified two previously known nonsense mutations and one novel likely pathogenic missense variant in PAX6 in probands by means of targeted NGS. The subsequent segregation analysis by Sanger sequencing evidenced the presence of highly probable mosaic events in paternal blood samples. Mosaicism was further confirmed by droplet digital PCR analysis in several somatic tissues of mosaic fathers. Quantification of the mutant allele fraction in parental samples showed a marked deviation from 50%, with a range between 12 and 29% depending on cell type. Gonosomal mosaicsm was definitively confirmed in one of the families thanks to the availability of a sperm sample from the mosaic father. Thus, the recurrence risk in this family was estimated to be about one-third. This is the first report confirming parental PAX6 mosaicism as a cause of disease recurrence in aniridia and other related phenotypes. In addition, we demonstrated that post-zygotic mosaicism is a frequent and underestimated pathogenic mechanism in aniridia, explaining intra-familial phenotypic variability in many cases. Our findings may have substantial implications for genetic counseling in congenital aniridia. Thus, we also highlight the importance of comprehensive genetic screening of parents for new sporadic cases with aniridia or related developmental eye disease to more accurately assess recurrence risk. In conclusion, somatic and/or gonosomal mosaicism should be taken into consideration as a genetic factor to explain not only families with unaffected parents despite multiple affected children but also variable expressivity, apparent de novo cases, and even uncharacterized cases of aniridia and related developmental eye disorders, apparently lacking PAX6 mutations

A Novel Truncating Mutation in HOMER2 Causes Nonsyndromic Progressive DFNA68 Hearing Loss in a Spanish Family

Nonsyndromic hereditary hearing loss is a common sensory defect in humans that is clinically and genetically highly heterogeneous. So far, 122 genes have been associated with this disorder and 50 of them have been linked to autosomal dominant (DFNA) forms like DFNA68, a rare subtype of hearing impairment caused by disruption of a stereociliary scaffolding protein (HOMER2) that is essential for normal hearing in humans and mice. In this study, we report a novel HOMER2 variant (c.832_836delCCTCA) identified in a Spanish family by using a custom NGS targeted gene panel (OTO-NGS-v2). This frameshift mutation produces a premature stop codon that may lead in the absence of NMD to a shorter variant (p.Pro278Alafs*10) that truncates HOMER2 at the CDC42 binding domain (CBD) of the coiled-coil structure, a region that is essential for protein multimerization and HOMER2-CDC42 interaction. c.832_836delCCTCA mutation is placed close to the previously identified c.840_840dup mutation found in a Chinese family that truncates the protein (p.Met281Hisfs*9) at the CBD. Functional assessment of the Chinese mutant revealed decreased protein stability, reduced ability to multimerize, and altered distribution pattern in transfected cells when compared with wild-type HOMER2. Interestingly, the Spanish and Chinese frameshift mutations might exert a similar effect at the protein level, leading to truncated mutants with the same Ct aberrant protein tail, thus suggesting that they can share a common mechanism of pathogenesis. Indeed, age-matched patients in both families display quite similar hearing loss phenotypes consisting of early-onset, moderate-to-profound progressive hearing loss. In summary, we have identified the third variant in HOMER2, which is the first one identified in the Spanish population, thus contributing to expanding the mutational spectrum of this gene in other populations, and also to clarifying the genotype–phenotype correlations of DFNA68 hearing loss

Hypothesizing an Ancient Greek Origin of the GJB2 35delG Mutation: Can Science Meet History?

One specific mutation of the GJB2 gene that encodes the connexin 26 protein, the 35delG mutation, has become a major interest among scientists who focus on the genetics of nonsyndromic hearing loss. The mutation accounts for the majority of GJB2 mutations detected in Caucasian populations and represents one of the most frequent disease mutations identified so far. The debate was so far between the arguments whether or not the 35delG mutation constitutes a mutational hot-spot or a founder effect; however, it was recently clarified that the latter seems the most likely. In an attempt to explore the origin and propagation of the 35delG mutation, several groups have reported the prevalence of the mutation and the carrier rates in different populations worldwide. It is now certain that the theory of a common founder prevails and that the highest carrier frequencies of the 35delG mutation are observed in southern European populations, giving rise to a discussion regarding the origin of the 35delG mutation. In this study, we discuss data previously published by our and other groups and also compare the haplotype distribution of the mutation in southern Europe, trying to understand the pathways of science and history and the conflict between them

A novel splice-site mutation in the GJB2 gene causing mild postlingual hearing impairment.

The DFNB1 subtype of autosomal recessive, nonsyndromic hearing impairment, caused by mutations affecting the GJB2 (connexin-26) [corrected] gene, is highly prevalent in most populations worldwide. DFNB1 hearing impairment is mostly severe or profound and usually appears before the acquisition of speech (prelingual onset), though a small number of hypomorphic missense mutations result in mild or moderate deafness of postlingual onset. We identified a novel GJB2 splice-site mutation, c. -22-2A>C, in three siblings with mild postlingual hearing impairment that were compound heterozygous for c. -22-2A>C and c.35delG. Reverse transcriptase-PCR experiments performed on total RNA extracted from saliva samples from one of these siblings confirmed that c. -22-2A>C abolished the acceptor splice site of the single GJB2 intron, resulting in the absence of normally processed transcripts from this allele. However, we did isolate transcripts from the c. -22-2A>C allele that keep an intact GJB2 coding region and that were generated by use of an alternative acceptor splice site previously unknown. The residual expression of wild-type connexin-26 [corrected] encoded by these transcripts probably underlies the mild severity and late onset of the hearing impairment of these subjects

Hearing impairment in family S1599.

<p><b>A</b> Pedigree of family S1599, indicating the <i>GJB2</i> genotypes of subjects who were analyzed. B Audiograms (air conduction) of affected individuals II:1 and II:6 at ages 50 and 31 years, respectively (circles, right ear; crosses, left ear). The binaural means of the hearing thresholds for air conduction at frequencies 0.5, 1, and 2 kHz for these subjects are 33.3 and 25.8 dB, respectively, corresponding to mild HI (21-40 dB).</p

Sequence of the exon-intron junctions of the single <i>GJB2</i> intron.

<p>Exonic sequence is shown in capitals, whereas intronic sequence is shown in lowercase italics. The three acceptor splice sites identified in this work appear boxed in bold: KS, known acceptor site; AS1, alternative site 1; AS2, alternative site 2. The ATG start codon appears in bold. Nucleotides affected by the c. -22-2A>C and c.35delG mutations are indicated by arrows. Locations of the primers used for identifying <i>GJB2</i> splicing products are underlined.</p