The Autism Diagnostic Interview-Revised and the Childhood Autism Rating Scale: Differences Between Diagnostic Systems and Comparison Between Genders

Diagnoses for autism based on the Autism Diagnostic Interview-Revised (ADI-R) and the Childhood Autism Rating Scale (CARS) were examined for 83 individuals with suspected autism. Agreement between systems reached 85.7%. Participants receiving diagnosis of autism based on only one system were significantly younger in age than individuals receiving diagnoses according to both systems. Individuals who did not receive diagnosis of autism on the ADI-R had lower chronological and mental ages and lower CARS scores compared to individuals who received diagnosis of autism based on the ADI-R. Eighteen females and 18 males were matched to examine possible gender differences. No significant findings were revealed, suggesting that the symptoms of autism according to the ADI-R and CARS do not differ between males and females when matched for chronological and mental ages.     

Recombinant mapping of the familial hyperinsulinism gene to an 0.8 cM region on chromosome 11p15.1 and demonstration of a founder effect in Ashkenazi Jews

A gene for autosomal recessive familial hyperinsulinism (HI)(OMIM: 256450 [OMIM] ), a neonatal metabolic disease characterized byinappropriate insulin secretion In the presence of severe hypoglycemia,was recently mapped to a 6.6 cM interval between the markersD11S926 and D11S928 on chromosome lip In 15 families (1). inthe current study we evaluated six additional families and fivenew markers, and further localized the gene between D11S419and D11S131O. Using genotype data from CEPH Version 7 and datagenerated from this study, this region was estimated to be 0.8cM in length. Significant linkage disequilib rium between markersand the HI gene was observed over a region of 10.3 cM (11pter-D11S926-D11S1308-11pcen)for Ashkenazi Jewish chromosomes. Haplotype analysis showedthat 12 of 36 HI chromosomes, versus one of 36 non-HI chromosomes, bore a specific haplotype for D11S419-D11 S902-D11 S921(p<0.0007), strongly suggesting a founder eftect In thisethnic group.     

Factor XI deficiency in French Basques is caused predominantly by an ancestral Cys38Arg mutation in the factor XI gene

Inherited factor XI deficiency is an injury-related bleeding disorder that is rare in most populations except for Jews, in whom 2 mutations, a stop mutation in exon 5 (type II) and a missense mutation in exon 9 (type III), predominate. Recently, a cluster of 39 factor XI-deficient patients was described in the Basque population of Southwestern France. In this study, we determined the molecular basis of factor XI deficiency in 16 patients belonging to 12 unrelated families of French Basque origin. In 8 families, a nucleotide 209T>C transition in exon 3 was detected that predicts a Cys38Arg substitution. Four additional novel mutations in the factor XI gene, Cys237Tyr, Tyr493His, codon 285delG, and IVS6 + 3A>G, were identified in 4 families. Expression studies showed that Cys38Arg and Cys237Tyr factor XI were produced in transfected baby hamster kidney cells, but their secretion was impaired. Cells transfected with Tyr493His contained reduced amounts of factor XI and displayed decreased secretion. A survey of 206 French Basque controls for Cys38Arg revealed that the prevalence of the mutant allele was 0.005. Haplotype analysis based on the study of 10 intragenic polymorphisms was consistent with a common ancestry (a founder effect) for the Cys38Arg mutation.     

Differential gonadotropin-releasing hormone (GnRH) and GnRH receptor messenger ribonucleic acid expression patterns in different tissues of the female rat across the estrous cycle

GnRH, the main regulator of reproduction, is produced in a variety of tissues outside of the hypothalamus, its main site of synthesis and release. We aimed to determine whether GnRH produced in the female rat pituitary and ovaries is involved in the processes leading to ovulation. We studied the expression patterns of GnRH and GnRH receptor (GnRH-R) in the same animals throughout the estrous cycle using real-time PCR. Hypothalamic levels of GnRH mRNA were highest at 1700 h on proestrus, preceding the preovulatory LH surge. No significant changes in the level of hypothalamic GnRH-R mRNA were detected, although fluctuations during the day of proestrus are evident. High pituitary GnRH mRNA was detected during the day of estrus, in the morning of diestrus 1, and at noon on proestrus. Pituitary GnRH-R displayed a similar pattern of expression, except on estrus, when its mRNA levels declined. Ovarian GnRH mRNA levels increased in the morning of diestrus 1 and early afternoon of proestrus. Here, too, GnRH-R displayed a somewhat similar pattern of expression to that of its ligand. To the best of our knowledge, this is the first demonstration of a GnRH expression pattern in the pituitary and ovary of any species. The different timings of the GnRH peaks in the three tissues imply differential tissue-specific regulation. We believe that the GnRH produced in the anterior pituitary and ovary could play a physiological role in the preparation of these organs for the midcycle gonadotropin surge and ovulation, respectively, possibly via local GnRH-gonadotropin axes.     

Nuclear localization signal binding protein from Arabidopsis mediates nuclear import of Agrobacterium VirD2 protein

T-DNA nuclear import is a central event in genetic transformation of plant cells by Agrobacterium. Presumably, the T-DNA transport intermediate is a single-stranded DNA molecule associated with two bacterial proteins, VirD2 and VirE2, which most likely mediate the transport process. While VirE2 cooperatively coats the transported single-stranded DNA, VirD2 is covalently attached to its 5′ end. To better understand the mechanism of VirD2 action, a cellular receptor for VirD2 was identified and its encoding gene cloned from Arabidopsis. The identified protein, designated AtKAPα, specifically bound VirD2 in vivo and in vitro. VirD2–AtKAPα interaction was absolutely dependent on the carboxyl-terminal bipartite nuclear localization signal sequence of VirD2. The deduced amino acid sequence of AtKAPα was homologous to yeast and animal nuclear localization signal-binding proteins belonging to the karyopherin α family. Indeed, AtKAPα efficiently rescued a yeast mutant defective for nuclear import. Furthermore, AtKAPα specifically mediated transport of VirD2 into the nuclei of permeabilized yeast cells.     

Autism Diagnostic Interview-Revised (ADI-R) Algorithms for Toddlers and Young Preschoolers: Application in a Non-US Sample of 1,104 Children

Journal of Autism and Developmental Disorders - The current study aimed to investigate the Autism Diagnostic Interview-Revised (ADI-R) algorithms for toddlers and young preschoolers (Kim and Lord,...     

The clinical and laboratory spectrum of dedicator of cytokinesis 8 immunodeficiency syndrome in patients with a unique mutation

Mutations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency usually diagnosed as autosomal recessive hyper IgE syndrome. We sought to reveal the varying manifestations in patients with a unique mutation in DOCK8 gene by a retrospective medical record review. Ten patients from five consanguineous families and three tribes were included. Seven patients were homozygous for the c.C5134A, p.S1711X mutation, and the remaining three patients were their siblings manifesting hyper IgE syndrome features without a genetic diagnosis. Prior to the genetic diagnosis, the clinical diagnosis was “hyper IgE syndrome” in six patients and “anti-pneumococcal antibody deficiency,” “recurrent pneumonia with bronchiectasis,” and “asthma with hypereosinophilic syndrome” each diagnosed once. One additional patient was diagnosed due to family history. The age of presentation varied from 1 to 16 months. Eczema was diagnosed in all patients, food allergies in three, and severe herpes keratitis or malignancy or autoimmunity in two patients. Elevated IgE was recorded in nine patients; however, in six patients, the initial serum IgE concentration was equal to or less than three times the normal concentration for age, and in these patients, the median age at IgE evaluation was 7.5 months compared with 21.5 months in patients with an initial IgE concentration above three times the normal concentration for age (P = 0.067). The spectrum of disease manifestations in patients with a unique mutation in DOCK8 is variable. The genotype-phenotype correlations may be modified by genetic and/or epigenetic modifiers beyond the monogenic effect. Younger patients tend to have lower IgE concentrations at the initial measurement of IgE.