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Barth syndrome (BTHS) is a lethal rare genetic disorder, which results in cardiac dysfunction, severe skeletal muscle weakness, immune issues and growth delay. Mutations in the TAFAZZIN gene, which is responsible for the remodeling of the phospholipid cardiolipin (CL), lead to abnormalities in mitochondrial membrane, including alteration of mature CL acyl composition and the presence of monolysocardiolipin (MLCL). The dramatic increase in the MLCL/CL ratio is the hallmark of patients with BTHS, which is associated with mitochondrial bioenergetics dysfunction and altered membrane ultrastructure. There are currently no specific therapies for BTHS. Here, we showed that cardiac mitochondria isolated from TAFAZZIN knockdown (TazKD) mice presented abnormal ultrastructural membrane morphology, accumulation of vacuoles, pro-fission conditions and defective mitophagy. Interestingly, we found that in vivo treatment of TazKD mice with a CL-targeted small peptide (named SS-31) was able to restore mitochondrial morphology in tafazzin-deficient heart by affecting specific proteins involved in dynamic process and mitophagy. This agrees with our previous data showing an improvement in mitochondrial respiratory efficiency associated with increased supercomplex organization in TazKD mice under the same pharmacological treatment. Taken together our findings confirm the beneficial effect of SS-31 in the amelioration of tafazzin-deficient dysfunctional mitochondria in a BTHS animal model. [ABSTRACT FROM AUTHOR]

Neurons are highly dependent on mitochondria to meet their bioenergetic needs and understanding the metabolic changes during the differentiation process is crucial in the neurodegeneration context. Several in vitro approaches have been developed to study neuronal differentiation and bioenergetic changes. The human SH-SY5Y cell line is a widely used cellular model and several differentiation protocols have been developed to induce a neuron-like phenotype including retinoic acid (RA) treatment. In this work we obtained a homogeneous functional population of neuron-like cells by a two-step differentiation protocol in which SH-SY5Y cells were treated with RA plus the mitotic inhibitor 2-deoxy-5-fluorouridine (FUdr). RA-FUdr treatment induced a neuronal phenotype characterized by increased expression of neuronal markers and electrical properties specific to excitable cells. In addition, the RA-FUdr differentiated cells showed an enrichment of long chain and unsaturated fatty acids (FA) in the acyl chain composition of cardiolipin (CL) and the bioenergetic analysis evidences a high coupled and maximal respiration associated with high mitochondrial ATP levels. Our results suggest that the observed high oxidative phosphorylation (OXPHOS) capacity may be related to the activation of the cyclic adenosine monophosphate (cAMP) pathway and the assembly of respiratory supercomplexes (SCs), highlighting the change in mitochondrial phenotype during neuronal differentiation. [ABSTRACT FROM AUTHOR]

Epidemiological data show that men and women have similar probabilities of contracting COVID-19. However, men with COVID-19 tend to have more severe outcomes than women. We performed two studies to analyze the associations between gender, adherence to traditional masculinity ideology, perceived vulnerability to COVID-19, and the adoption of protective behaviors against COVID-19. In Study 1 (quota sample of the Italian adult population, N = 1,142), we found no differences between men and women in terms of the perceived probability of contracting COVID-19. However, compared to women, men perceived themselves to be less likely to suffer severe consequences if falling ill. In Study 2 (Italian community sample, N = 305), a moderated mediation model showed that adherence to traditional masculinity ideology moderated the association between being man and the perceived severity of the consequences of COVID-19, which, in turn, showed negative associations with three protective behaviors against COVID-19. The article ends with a discussion of the strengths and limitations of this research. [ABSTRACT FROM AUTHOR]

Barth Syndrome (BTHS), a genetic disease associated with early-onset cardioskeletal myopathy, is caused by loss-of-function mutations of the TAFAZZIN gene, which is responsible for remodeling the mitochondrial phospholipid cardiolipin (CL). Deregulation of CL biosynthesis and maturation in BTHS mitochondria result in a dramatically increased monolysocardiolipin (MLCL)/CL ratio associated with bioenergetic dysfunction. One of the most promising therapeutic approaches for BTHS includes the mitochondria-targeted tetrapeptide SS-31, which interacts with CL. Here, we used TAFAZZIN knockdown (TazKD) mice to investigate for the first time whether in vivo administration of SS-31 could affect phospholipid profiles and mitochondrial dysfunction. The CL fingerprinting of TazKD cardiac mitochondria obtained by MALDI-TOF/MS revealed the typical lipid changes associated with BTHS. TazKD mitochondria showed lower respiratory rates in state 3 and 4 together with a decreased in maximal respiratory rates. Treatment of TazKD mice with SS-31 improved mitochondrial respiratory capacity and promoted supercomplex organization, without affecting the MLCL/CL ratio. We hypothesize that SS-31 exerts its effect by influencing the function of the respiratory chain rather than affecting CL directly. In conclusion, our results indicate that SS-31 have beneficial effects on improving cardiac mitochondrial dysfunction in a BTHS animal model, suggesting the peptide as future pharmacologic agent for therapy. [ABSTRACT FROM AUTHOR]

Rubinstein-Taybi syndrome (RSTS) is a rare multisystem developmental disorder with moderate to severe intellectual disability caused by heterozygous mutations of either CREBBP or EP300 genes encoding CBP/p300 chromatin regulators. We explored the gene programs and processes underlying the morphological and functional alterations shown by iPSC-derived neurons modeling RSTS to bridge the molecular changes resulting from defective CBP/p300 to cognitive impairment. By global transcriptome analysis, we compared the differentially expressed genes (DEGs) marking the transition from iPSC-derived neural progenitors to cortical neurons (iNeurons) of five RSTS patients carrying private CREBBP/EP300 mutations and manifesting differently graded neurocognitive signs with those of four healthy controls. Our data shows a defective and altered neuroprogenitor to neuron transcriptional program in the cells from RSTS patients. First, transcriptional regulation is weaker in RSTS as less genes than in controls are modulated, including genes of key processes of mature functional neurons, such as those for voltage-gated channels and neurotransmitters and their receptors. Second, regulation is subverted as genes acting at pre-terminal stages of neural differentiation in cell polarity and adhesive functions (members of the cadherin family) and axon extension/guidance (members of the semaphorins and SLIT receptors families) are improperly upregulated. Impairment or delay of RSTS neuronal differentiation program is also evidenced by decreased modulation of the overall number of neural differentiation markers, significantly impacting the initial and final stages of the differentiation cascade. Last, extensive downregulation of genes for RNA/DNA metabolic processes confirms that RSTS is a global transcription disorder, consistent with a syndrome driven by chromatin dysregulation. Interestingly, the morphological and functional alterations we have previously appointed as biomarkers of RSTS iNeurons provide functional support to the herein designed transcriptome profile pointing to key dysregulated neuronal genes as main contributors to patients' cognitive deficit. The impact of RSTS transcriptome may go beyond RSTS as comparison of dysregulated genes across modeled neurodevelopmental disorders could unveil convergent genes of cognitive impairment. [ABSTRACT FROM AUTHOR]

As there is a robust tendency to support system-legitimizing beliefs by appealing to stereotypes or ideologies, we examined the role played by the perception of the status quo in relation to the infrahumanization bias. We compared this bias in high versus low-status group members and tested the mediating role of system justification beliefs and ingroup identification. The results of a moderated-mediated regression model (N = 238) showed that the perception of legitimacy of one's own status had differential effects on the infrahumanization bias: The perception of legitimacy was positively associated with the endorsement of system justification beliefs and negatively associated with ingroup identification among low-status group members, whereas the perception of legitimacy was positively associated with ingroup identification among high-status group members. In both groups, ingroup identification was positively correlated with the tendency to infrahumanize the outgroup, while the endorsement of system justification beliefs was linked to the infrahumanization among low-status group members only. The findings highlight that the Social Identity Theory and the System Justification Theory can be fruitfully combined to explain infrahumanization tendencies. [ABSTRACT FROM AUTHOR]

Pathogenic variation in MAPT, GRN, and C9ORF72 accounts for at most only half of frontotemporal lobar degeneration (FTLD) cases with a family history of neurological disease. This suggests additional variants and genes that remain to be identified as risk factors for FTLD. We conducted a case-control genetic association study comparing pathologically diagnosed FTLD patients (n = 94) to cognitively normal older adults (n = 3541), and found suggestive evidence that gene-wide aggregate rare variant burden in MFSD8 is associated with FTLD risk. Because homozygous mutations in MFSD8 cause neuronal ceroid lipofuscinosis (NCL), similar to homozygous mutations in GRN, we assessed rare variants in MFSD8 for relevance to FTLD through experimental follow-up studies. Using post-mortem tissue from middle frontal gyrus of patients with FTLD and controls, we identified increased MFSD8 protein levels in MFSD8 rare variant carriers relative to non-variant carrier patients with sporadic FTLD and healthy controls. We also observed an increase in lysosomal and autophagy-related proteins in MFSD8 rare variant carrier and sporadic FTLD patients relative to controls. Immunohistochemical analysis revealed that MFSD8 was expressed in neurons and astrocytes across subjects, without clear evidence of abnormal localization in patients. Finally, in vitro studies identified marked disruption of lysosomal function in cells from MFSD8 rare variant carriers, and identified one rare variant that significantly increased the cell surface levels of MFSD8. Considering the growing evidence for altered autophagy in the pathogenesis of neurodegenerative disorders, our findings support a role of NCL genes in FTLD risk and suggest that MFSD8-associated lysosomal dysfunction may contribute to FTLD pathology. [ABSTRACT FROM AUTHOR]

Political interest is a key for the survival and development of democracies. Therefore, it is important to establish when political interest develops. We examined changes in political interest-when and in which directions-among youths between 13 and 28 years of age. We followed five age groups of Swedish youths over 2 years, with a total of 2621 participants. Analysis of stability coefficients supported the idea that political interest becomes more stable with age. From their early twenties, youths' political interest was found to be as stable as has been earlier reported for adults. Among adolescents, the lowest stability rate was observed in the youngest cohort (ages 13-15). The results also showed that, when taking the increase in political interest into account, the proportion of youths losing their interest in politics corresponded to the proportion of youths gaining interest over time. On the whole, this study brings new insights on the development of political interest over time. It provides empirical evidence on when political interest is most susceptible to change and on how it is likely to change. Implications for research and intervention are discussed. [ABSTRACT FROM AUTHOR]

The main aim of this study was to investigate the relations between basic personal values, drawn on Schwartz's value theory, and the expression of the individual fear of crime by analysing the moderating role of contextual cues (i.e., crime rates). We performed a multinational, multilevel study using the 2008 European Social Survey dataset ( N = 53,692, nested in 27 European countries). The fear of crime, which is a generalised insecurity about personal safety, showed a positive association with conservation (i.e., tradition, conformity and security) and a negative association with openness to change (i.e., hedonism, stimulation and self-direction) and self-transcendence values (i.e., benevolence and universalism). With the exception of self-transcendence, all the associations between basic values and the fear of crime were amplified by the country's crime rate: the higher the crime rate, the stronger the relation between values and the fear of crime. The implications and limitations of these results and possible further research directions are discussed. [ABSTRACT FROM AUTHOR]

Social psychologists have explored the multiple forms of status quo legitimization mainly in regard to the social and economic system. This study aimed to explore the tendency to legitimize the political system by developing and validating a scale of democratic system justification (DSJ). We administered a scale composed of 8 items, mainly derived from the extant system justification scales (Jost and Thompson in J Exp Soc Psychol, 3:209-232, ; Kay and Jost in J Pers Soc Psychol, 85:823-837, ; Jost and Kay in J Pers Soc Psychol, 88:498-509, ; Jost et al. in Dubois Rev Soc Sci Race, 6:103-124, ) to an Italian sample of 205 participants. Exploratory and confirmatory factor analyses indicated that the scale has a one-dimensional structure. Results also showed that internal reliability of the scale was good; moreover, correlational analyses and group comparisons confirmed the convergent and discriminant validity of the scale. Implications for the assessment of the DSJ and future directions of research on this topic are discussed. [ABSTRACT FROM AUTHOR]

In a national sample of the Italian population, surveyed four times between October 2002 and January 2007 ( N = 2,008), we performed a multilevel longitudinal study aimed at predicting the increase in crime risk perception as a function of three families of independent variables, respectively lying at the within individual level (direct victimization and indirect victimization), at the between-individuals level (being a woman, being an older person, being a poorly educated person and size of area of residence) and at the ecological level (county's crime rate, unemployment rate and immigration rate). Direct and indirect victimization, being a woman, being an older person, living in a large town and in a context characterized by high crime and unemployment rates positively influenced the change in crime risk perception, while the other individual and ecological predictors we used in our predictive model did not. Strengths, limitations, implications and future developments of this research are discussed. [ABSTRACT FROM AUTHOR]

The studies presented here focus on the relationship between legitimizing ideologies and ambivalent sexism. 544 Italian students (Study 1) and 297 US students (Study 2) completed several scales: social dominance orientation (SDO), system justification (SJ), political orientation, religiosity, and the Glick and Fiske (J Pers Soc Psychol 70(3):491-512, ) Ambivalent Sexism Inventory. Zero-order correlations revealed all facets of ideological attitudes to be positively related to each other and correlated with ambivalent sexism. In particular, the SDO was related to both ideology components of SJ and political orientation and to ambivalent sexism (hostile and benevolent). Moderated regressions revealed that SDO has a positive impact on hostile sexism for men only, while SJ has a positive impact on hostile sexism for women only. While the first result was stable across the two studies, the last moderated effect has been detected only in Study 1. We discuss the results with respect to different facets of social ideologies and cultural differences between the two countries. [ABSTRACT FROM AUTHOR]

Cornelia de Lange syndrome (CdLS) is a rare multisystemic congenital anomaly disorder that is characterised by intellectual disability and growth retardation, congenital heart defects, intestinal anomalies, facial dysmorphism (including synophyris and high arched eyebrows) and limb reduction defects. Mutations in three cohesin-associated genes encoding a key regulator (NIPBL, chr 5p13.2) and one structural component of the cohesin ring (SMC1A, chr Xp11) occur in about 65% of CdLS patients. NIPBL is the major causative gene, and accounts for 40-60% of CdLS patients as shown by a number of mutational screening studies that indicate a wide mutational repertoire of mainly small deletions and point mutations. Only a few data are available concerning the occurrence of large NIPBL rearrangements or intragenic deletions or duplications involving whole exons. We used multiplex ligation-dependent probe amplification (MLPA) to study 132 CdLS patients negative to the standard mutation NIPBL test out of a cohort of 200 CdLS patients. A total of 7 out of 132 patients were found to carry NIPBL alterations, including two large gene deletions extending beyond the gene, four intragenic multi- or single-exon deletions and one single-exon duplication. These findings show that MLPA leads to a 5.3% increase in the detection of mutations when used in addition to the standard NIPBL scan, and contributes per se to the molecular diagnosis of 3.5% (7/200) of clinically diagnosed CdLS patients. It is recommended that MLPA be included in the CdLS diagnostic flow chart. [ABSTRACT FROM AUTHOR]

Beckwith-Wiedemann syndrome (BWS), an overgrowth disorder with several congenital abnormalities, encompasses nephrourological anomalies. The objective of the report is to analyze the latter and related genotype-phenotype correlations. The study was a retrospective review of nephrourological investigations and genotype in 67 BWS patients. Imaging and laboratory studies have been correlated with the molecular anomalies typical of BWS. Thirty-eight (56.7%) patients had a total of 61 nonmalignant nephrourological findings, including nephromegaly ( n = 24), collecting system abnormalities ( n = 14), cryptorchidism ( n = 11), nephrolithiasis ( n = 5), cysts ( n = 5), and dysplasia ( n = 1). Four patients had Wilms' tumor, all associated with renal hyperplasia. Renal findings were almost consistent in the BWS group, with nephromegaly in all patients and collecting system abnormalities in half of them. BWS and negative patients also had frequent anomalies (63.6% and 61.9% respectively), whereas only 36.0% of BWS had renal findings ( p = 0.003). Cryptorchidism was associated with abdominal wall defects ( p < 0.001) appearing more frequently in BWS ( p = 0.028). Urinary tract infections were observed in 17.9% of patients, with two resulting in life-threatening sepsis. Hypercalciuria was present in 10% of cases. 55.5% of BWS patients have renal findings. Although variegate, these anomalies disclose a genotype-phenotype correlation. [ABSTRACT FROM AUTHOR]

Genomic imprinting is an epigenetic phenomenon restricting gene expression in a manner dependent on parent of origin. Imprinted gene products are critical regulators of growth and development, and imprinting disorders are associated with both genetic and epigenetic mutations, including disruption of DNA methylation within the imprinting control regions (ICRs) of these genes. It was recently reported that some patients with imprinting disorders have a more generalised imprinting defect, with hypomethylation at a range of maternally methylated ICRs. We report a cohort of 149 patients with a clinical diagnosis of Beckwith–Wiedemann syndrome (BWS), including 81 with maternal hypomethylation of the KCNQ1OT1 ICR. Methylation analysis of 11 ICRs in these patients showed that hypomethylation affecting multiple imprinted loci was restricted to 17 patients with hypomethylation of the KCNQ1OT1 ICR, and involved only maternally methylated loci. Both partial and complete hypomethylation was demonstrated in these cases, suggesting a possible postzygotic origin of a mosaic imprinting error. Some ICRs, including the PLAGL1 and GNAS/NESPAS ICRs implicated in the aetiology of transient neonatal diabetes and pseudohypoparathyroidism type 1b, respectively, were more frequently affected than others. Although we did not find any evidence for mutation of the candidate gene DNMT3L, these results support the hypotheses that trans-acting factors affect the somatic maintenance of imprinting at multiple maternally methylated loci and that the clinical presentation of these complex cases may reflect the loci and tissues affected with the epigenetic abnormalities.European Journal of Human Genetics (2009) 17, 611–619; doi:10.1038/ejhg.2008.233; published online 17 December 2008 [ABSTRACT FROM AUTHOR]

Linkage and cytogenetics studies have found the Angelman syndrome (AS) chromosomal region to be of relevance to autism disorder (AD) or autism spectrum disorder (ASD). Autism is considered part of the behavioural phenotype in AS based on formal autism assessments (autism diagnostic interview—revised [ADI-R] and autism diagnostic observation schedule [ADOS]), which have mainly addressed the deleted AS group. We explored 23 AS patients including all genetic subtypes and made a co-morbid diagnosis of AD/ASD in 14/23 (61%), which does not include 4 cases classified within the broader autism spectrum disorder (bASD). Deletions accounted for the main fraction (35%), ubiquitin-protein ligase E3A (UBE3A) mutation represented 13%, imprinting defects and uniparental disomy 9 and 4%, respectively. UBE3A mutations due to lack of the homologous to the E6-associated protein carboxyl terminus domain ( n = 3) were associated with the ASD, while more distal mutations ( n = 3) seem to escape from a co-morbid diagnosis of autism/autism spectrum. Differences in severity of autistic features were seen across subtypes of AS, with some behavioural features being unique to AS and some representing all forms of developmental disability. Autism signs (poor/lack of eye contact, showing, spontaneous initiation of joint attention, social quality of overtures [ADOS algorithm items for Diagnostic and Statistical Manual of Mental Disorders—IV (DSM-IV)/International Statistical Classification of Diseases and Related Health Problems—10 (ICD-10) autism diagnosis belonging to the reciprocal social interaction domain]) discriminating all the co-morbid AS categories from non-autistic AS belonged to the social interaction domain. Impairments in the communication domain (gestures, pointing, use of another’s body, frequency of vocalisation towards others [ADOS algorithm items for DSM-IV/ICD-10 autism diagnosis belonging to the communication domain]) justified classification of co-morbid AD/ASD vs the classification of less affected bASD. Evaluation of the behaviour domain suggested that repetitive sensory and motor behaviours correlate with a low developmental profile rather than being specific to autism. [ABSTRACT FROM AUTHOR]

Mental retardation (MR) is displayed by 57% of NF1 patients with microdeletion syndrome as a result of 17q11.2 region haploinsufficiency. We considered the cyclin-dependent kinase 5 regulatory subunit 1 ( CDK5R1) and oligodendrocyte-myelin glycoprotein ( OMG) genes, mapping in the NF1 microdeleted region, as candidate genes for MR susceptibility. CDK5R1 encodes for a neurone-specific activator of cyclin-dependent kinase 5 (CDK5) involved in neuronal migration during central nervous system development. OMG encodes for an inhibitor of neurite outgrowth by the binding to the Nogo-66 receptor (RTN4R). CDK5R1 and OMG genes are characterized by large 3′ and 5′ untranslated regions (UTRs), where we predict the presence of several transcription/translation regulatory elements. We screened 100 unrelated Italian patients affected by unspecific MR for mutations in CDK5R1 and OMG coding regions and in their 3′ or 5′ UTRs. Four novel mutations and two novel polymorphisms for CDK5R1 and three novel mutations for OMG were detected, including two missense changes (c.323C>T; A108V in CDK5R1 and c.1222A>G; T408A in OMG), one synonymous codon variant (c.532C>T; L178L in CDK5R1), four variants in CDK5R1 3′UTR and two changes in OMG 5′UTR. All the mutations were absent in 370 chromosomes from normal subjects. The allelic frequencies of the two novel polymorphisms in CDK5R1 3′UTR were established in both 185 normal and 100 mentally retarded subjects. Prediction of mRNA and protein secondary structures revealed that two changes lead to putative structural alterations in the mutated c.2254C>G CDK5R1 3′UTR and in OMG T408A gene product. [ABSTRACT FROM AUTHOR]

Nance-Horan syndrome (NHS) is an X-linked condition characterised by congenital cataracts, dental abnormalities, dysmorphic features, and mental retardation in some cases. Previous studies have mapped the disease gene to a 2 cM interval on Xp22.2 between DXS43 and DXS999. We report additional linkage data resulting from the analysis of eleven independent NHS families. A maximum Iod score of 9.94 (θ=0.00) was obtained at the RS1 locus and a recombination with locus DXS1195 on the teiomeric side was observed in two families, thus refining the location of the gene to an interval of around 1 Mb on Xp22.13. Direct sequencing or SSCP analysis of the coding exons of five genes (SCML1, SCML2, STK9, RS1 and PPEF1), considered as candidate genes on the basis of their location in the critical interval, failed to detect any mutation in 12 unrelated NHS patients, thus making it highly unlikely that these genes are implicated in NHS. [ABSTRACT FROM AUTHOR]

A cohort of 31 cystic fibrosis patients showing pancreatic sufficiency and bearing an unidentified mutation on at least one chromosome was analyzed through denaturing gradient gel electrophoresis of the whole coding region of the cystic fibrosis transmembrane conductance regulator gene, including intron-exon boundaries. Three new and 19 previously described mutations were detected. The combination of these with known mutations detected by other methods, allowed the characterization of mutations on 56/62 (90.3%) chromosomes. Among those identified, 17 can be considered responsible for pancreatic sufficiency, since they were found in patients carrying a severe mutation on the other chromosome. Among these presumed mild mutations, eight were detected more than once, R352Q being the most frequent in this sample (4.83%). Intragenic microsatellite analysis revealed that the six chromosomes still bearing unidentified mutations are associated with five different haplotypes. This may indicate that these chromosomes bear different mutations, rarely occurring among cystic fibrosis patients, further underlying the molecular heterogeneity of the genetic defects present in patients having pancreatic sufficiency. [ABSTRACT FROM AUTHOR]

Three polymorphic DNA markers surrounding the D7S8 locus were tested for their usefulness in the diagnosis of cystic fibrosis (CF) by linkage analysis. The markers correspond to the loci D7S424 and D7S426. These polymorphisms were studied by centers in the U.S., the United Kingdom, the Netherlands, and Italy, using samples from populations throughout Europe and North America. The additional information provided by these probes increased the heterogeneity of the region from 50% to 58% and was essential for a completely informative diagnosis in one family. A very high degree of linkage disequilibrium was found between these markers, which span a distance of approximately 250kb. In addition, linkage disequilibrium with CF was noted. Significant heterogeneity of linkage disequilibrium was found among the populations, both for the marker-marker pairs and between the markers and CF. [ABSTRACT FROM AUTHOR]

Cornelia de Lange syndrome is a multisystem developmental disorder characterized by facial dysmorphisms, upper limb abnormalities, growth delay and cognitive retardation. Mutations in the NIPBL gene, a component of the cohesin complex, account for approximately half of the affected individuals. We report here that mutations in SMC1L1 (also known as SMC1), which encodes a different subunit of the cohesin complex, are responsible for CdLS in three male members of an affected family and in one sporadic case. [ABSTRACT FROM AUTHOR]

A sample of 175 Italian cystic fibrosis patients has been analysed for the presence of the ΔF508 mutation. The frequency of this mutation among 137 patients with pancreatic insufficiency is equal to 57%; in 23 patients with pancreatic sufficiency it is 26%. A high proportion of the unknown mutations is associated with the same rare haplotype found in association with ΔF508, suggesting that at least another mutation occurred on a chromosome characterized by the same haplotype. [ABSTRACT FROM AUTHOR]