Associations of oxytocin receptor gene (
OXTR) variants and autism spectrum disorders (ASD) have been reported in earlier studies; in one of the studies associations with IQ and daily living skills ...were found additionally. Variations of the oxytocin receptor gene might also regulate affect, attachment and separation beyond the diagnostic borders of autism. We tested hypotheses of associations between positive and negative affects and social and emotional loneliness (285 adults), IQ (117 adolescents) and polymorphisms of the oxytocin receptor gene (
OXTR rs53576, rs2254298 and rs2228485) in normal subjects. Individuals with the oxytocin
OXTR rs53576 A/A genotype showed lower positive affect scores (
F
=
5.532, df
=
1;
p
=
0.019). This effect was restricted to males (
F
=
13.098, df
=
1;
p
=
0.00047). Haplotypes constructed with the three markers were associated with positive affect (
p
=
0.0012), negative affect (
p
<
0.0001) and emotional loneliness (
p
<
0.0001). Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents (
T
=
2.247,
p
=
0.027). Our findings support a role for the oxytocin receptor haplotypes in the generation of affectivity, emotional loneliness and IQ.
Abstract
Background/aims: The application of intranasal oxytocin enhances facial emotion recognition in normal subjects and in subjects with autism spectrum disorders (ASD). In addition, various ...features of social cognition have been associated with variants of the oxytocin receptor gene (OXTR). Therefore, we tested for associations between mind-reading, a measure for social recognition and OXTR polymorphisms. Methods: 76 healthy adolescents and young adults were tested for associations between OXTR rs53576, rs2254298, rs2228485 and mind-reading using the "Reading the Mind in the Eyes Test" (RMET). Results: After Bonferroni correction for multiple comparisons, rs2228485 was associated with the number of incorrect answers when subjects evaluated male faces (P =0.000639). There were also associations between OXTR rs53576, rs2254298 and rs2228485 and other RMET dimensions according to P <0.05 (uncorrected). Conclusion: This study adds further evidence to the hypothesis that genetic variations in the OXTR modulate mind-reading and social behaviour.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Restrictive dermopathy (RD) is a rare and extremely severe congenital genodermatosis, characterized by a tight rigid skin with erosions at flexure sites, multiple joint contractures, low bone density ...and pulmonary insufficiency generally leading to death in the perinatal period. RD is caused in most patients by compound heterozygous or homozygous ZMPSTE24 null mutations. This gene encodes a metalloprotease specifically involved in lamin A post-translational processing. Here, we report a total of 16 families for whom diagnosis and molecular defects were clearly established. Among them, we report seven new ZMPSTE24 mutations, identified in classical RD or Mandibulo-acral dysplasia (MAD) affected patients. We also report nine families with one or two affected children carrying the common, homozygous thymine insertion in exon 9 and demonstrate the lack of a founder effect. In addition, we describe several new ZMPSTE24 variants identified in unaffected controls or in patients affected with non-classical progeroid syndromes. In addition, this mutation update includes a comprehensive search of the literature on previously described ZMPSTE24 mutations and associated phenotypes. Our comprehensive analysis of the molecular pathology supported the general rule: complete loss-of-function of ZMPSTE24 leads to RD, whereas other less severe phenotypes are associated with at least one haploinsufficient allele.
The mutation detection rate for familial cerebral cavernous malformations (CCM) is extremely high, being about 90 % if direct sequencing of the three genes,
CCM1
,
CCM2
, and
CCM3
, is used in ...conjunction with quantitative analyses to detect larger
CCM1
-
3
deletions/duplications. We here report on an individual who had presented with more than 30 cerebral and spinal cavernous malformations, two intracranial meningiomas, and disease manifestation only in the mid-forties. A
CCM1
missense variant of unclear relevance was found during the first sequencing step. Thereafter, direct sequencing of all three
CCM
genes revealed the typical pathogenic loss-of-function mutation c.598C > T/p.Q200* in the
CCM3
gene. Our results demonstrate that mutation analyses of all three
CCM
genes in the index patient regardless of previous identification of an unclassified
CCM1
variant is crucial for reliable predictive testing of at-risk relatives.
Abstract Objective This study aimed to determine the contribution of EFHC1 variants to the phenotypic variability of juvenile myoclonic epilepsy (JME) and to evaluate their diagnostic value regarding ...previously identified clinical long-term seizure outcome predictors in a consecutive cohort of patients with JME. Methods Thirty-eight probands and three family members affected with JME were studied at a tertiary epilepsy center with a review of their medical records and a subsequent face-to-face interview. All coding EFHC1 exons and adjacent exon/intron boundaries were directly sequenced. Results The previously reported EFHC1 mutation F229L was found in two cases who presented with early generalized tonic–clonic seizure (GTCS) onset and appeared to be associated with milder subtypes of JME. Variant R294H was identified in two further probands who had a subtype of JME developing from childhood absence epilepsy. However, segregation of the phenotype with this variant could not be confirmed in one family. Conclusions Our findings corroborate the heterogeneity of JME as an electroclinical epilepsy syndrome and provide evidence that genetic factors may influence and help predict the long-term seizure outcome in patients with JME.
Cerebral cavernous malformations (CCM) are prevalent vascular malformations occurring in familial autosomal dominantly inherited or isolated forms. Once CCM are diagnosed by magnetic resonance ...imaging, the indication for genetic testing requires either a positive family history of cavernous lesions or clinical symptoms such as chronic headaches, epilepsy, neurological deficits, and hemorrhagic stroke or the occurrence of multiple lesions in an isolated case. Following these inclusion criteria, the mutation detection rates in a consecutive series of 105 probands were 87% for familial and 57% for isolated cases. Thirty‐one novel mutations were identified with a slight shift towards proportionally more CCM3 mutations carriers than previously published (CCM1: 60%, CCM2: 18%, CCM3: 22%). In‐frame deletions and exonic missense variants requiring functional analyses to establish their pathogenicity were rare: An in‐frame deletion within the C‐terminal FERM domain of CCM1 resulted in decreased protein expression and impaired binding to the transmembrane protein heart of glass (HEG1). Notably, 20% of index cases carrying a CCM mutation were below age 10 and 33% below age 18 when referred for genetic testing. Since fulminant disease courses during the first years of life were observed in CCM1 and CCM3 mutation carriers, predictive testing of minor siblings became an issue.
Stringent inclusion criteria, comprehensive molecular genetic testing of CCM1, CCM2, and CCM3 and subsequent functional analysis yield very high mutation detection rates for familial and isolated cerebral cavernous malformations (CCM). Notably, 20% of index cases carrying a CCM mutation were below age 10 and 33% below age 18 when referred for genetic testing. In particular, parents of children with severe disease courses request predictive genetic testing of siblings.
Both reduced postsynaptic dopamine D(2) receptor function and the character variable self-directedness (SDD) are related to the level of alcohol consumption. We examined for interactions between DRD2 ...exon 8(rs6276), a polymorphism which has been associated with various alcohol-related phenotypes, SDD and alcohol consumption.
A total of 144 male and 186 female probands with alcohol dependence or abuse diagnoses and without were included in the study. All subjects were assessed with the alcohol section of the Semi-Structured Assessment for the Genetics of Alcoholism and the Temperament and Character Inventory.
Male probands with A/A genotype reported significantly higher alcohol consumption in a typical week (ANOVA; p = 0.024); those with A/A genotype and low SDD showed particularly high consumption levels (interaction DRD2 x SDD: p = 0.019). Alcohol dependence/abuse (DSM-IV) but not nicotine dependence was also relevant for higher alcohol consumption (trend: p = 0.052). In the female group, only alcohol disorders predicted alcohol consumption.
Our findings support a role for a gene-personality interaction of DRD2 exon 8 x SDD in alcohol consumption in males.
Hemophilia A (HA) is X-chromosome linked bleeding disorders caused by deficiency of the coagulation factor VIII. The disease is caused by Factor VIII gene intron 22 inversion in approximately 50% of ...the patients and by intron 1 inversion in 5% of the patients. Both inversions occur as a result of intrachromosomal recombination between homologous region, in intron 1 or 22 and their extragenic copy located telomeric to the FVIII gene. The goal of the present study was to analyze the presence of these mutations in 15 HA severe Costarrican families.
Methods: We studied 122 unrelated HA patients and obligate or possible carriers for the presence of intron 22 or intron 1 by Southern blotting and polymerase chain reaction (PCR).
Results: We found altered intron 22 restriction profiles by Southern analyses in 14 of the families, 12 cases type 1 (Figure 1) and 2 cases type 2 inversion. During the screening for intron 1 inversion among the HA patient, who were intron 22 inversion negative, we did not identified this mutation.
Interpretation and Conclusions: This report is the first in our haemophilia families dealing with mutations in the intron 22 and intron 1. Our data highlight the importance of the analysis of intron 22 inversion for the association with development of inhibitors in the HA patients and we are continuous searching of intron 1 mutation. This will benefit both genetic counselling and the study of the relationship between genotype and inhibitor development.
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