A review of structural brain abnormalities in Pallister-Killian syndrome.

Background: Pallister-Killian syndrome (PKS) is a rare multisystem developmental syndrome usually caused by mosaic tetrasomy of chromosome 12p that is known to be associated with neurological defects.

Methods: We describe two patients with PKS, one of whom has bilateral perisylvian polymicrogyria (PMG), the other with macrocephaly, enlarged lateral ventricles and hypogenesis of the corpus callosum. We have also summarized the current literature describing brain abnormalities in PKS.

Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder.

Background: Autism spectrum disorders (ASDs) are complex, pervasive, and heterogeneous neurodevelopmental conditions with varying trajectories, significant male bias and largely unknown etiology. However, an understanding of the biological mechanisms driving pathophysiology is evolving. Immune system aberrations, as identified through cytokine profiles, are believed to have a role in ASD.

Reinforcing the association between distal 1q CNVs and structural brain disorder: A case of a complex 1q43-q44 CNV and a review of the literature.

Copy Number Variations (CNVs) comprising the distal 1q region 1q43-q44 are associated with neurological impairments, structural brain disorder, and intellectual disability. Here, we report an extremely rare, de novo case of a 1q43-q44 deletion with an adjacent duplication, associated with severe seizures, microcephaly, agenesis of the corpus callosum, and pachygyria, a consequence of defective neuronal migration disorder. We conducted a literature survey to find that our patient is only the second case of such a 1q43-q44 CNV ever to be described.

Development and validation of a family history screening questionnaire in Australian primary care.

Purpose: We aimed to validate a family history screening questionnaire in an Australian primary care population designed to identify people at increased risk for breast, ovarian, colorectal, and prostate cancer; melanoma; ischemic heart disease; and type 2 diabetes.

Methods: We prospectively validated the questionnaire in 6 general practices in Perth, Western Australia among 526 patients aged 20 to 50 years who responded to a single invitation from their general practice. They completed the 15-item questionnaire before a reference standard 3-generation pedigree was obtained by a genetic counselor blinded to the questionnaire responses.

Brief report: do the nature of communication impairments in autism spectrum disorders relate to the broader autism phenotype in parents?

Extensive empirical evidence indicates that the lesser variant of Autism Spectrum Disorders (ASD) involves a communication impairment that is similar to, but milder than, the deficit in clinical ASD. This research explored the relationship between the broader autism phenotype (BAP) among parents, an index of genetic liability for ASD, and proband communication difficulties. ASD probands with at least one BAP parent (identified using the Autism Spectrum Quotient) had greater structural and pragmatic language difficulties (assessed using the Children's Communication Checklist-2) than ASD probands with no BAP parent.

SNP-based arrays complement classic cytogenetics in the detection of chromosomal aberrations in Wilms' tumor.

Wilms' tumors have characteristic chromosomal abnormalities, such as the 11p13 deletion, in a subset of cases. This is one of the very few reports comparing single nucleotide polymorphism (SNP) array analysis with conventional karyotyping of Wilms' tumors. A total of 43 frozen tumor samples were analyzed using the Affymetrix Cytogenetics Whole-Genome 2.

Quality standards and samples in genetic testing.

The most critical performance indicator for medical laboratories is the delivery of accurate test results. In any laboratory, there is always the possibility that random or systematic errors may occur and place human health and welfare at risk. Laboratory quality assurance programmes continue to drive improvements in analytical accuracy.

A retrospective audit of family history records in short-stay medical admissions.

Objective: To retrospectively review the frequency and adequacy of family histories recorded from patients admitted to a short-stay medical unit in a tertiary teaching hospital.

Design, Setting And Patients: A formal audit of the medical records of 300 randomly selected patients who were admitted to the Royal Perth Hospital short-stay medical unit between July and December 2007.

Main Outcome Measure: Proportion of patient records with family history documents.

Linking MECP2 and pain sensitivity: the example of Rett syndrome.

Recent animal studies suggest links between MeCP2 function and sensitivity to pain. This study investigated the nature and prevalence of atypical pain responses in Rett syndrome and their relationships with specific MECP2 mutations. Families enrolled in the Australian Rett Syndrome Database (ARSD) and InterRett database participated in this study.

Maternal family history of diabetes is associated with a reduced risk of cardiovascular disease in women with type 2 diabetes: the Fremantle Diabetes Study.

Objective: To investigate whether parental family history of diabetes influences cardiovascular outcomes in type 2 diabetes.

Research Design And Methods: We studied 1,294 type 2 diabetic patients (mean age 64.1 years, 51.

Cells of epithelial lineage are present in blood, engraft the bronchial epithelium, and are increased in human lung transplantation.

Background: There is a growing expectation that cell-based therapies will prove effective for a wide range of conditions including lung diseases such as cystic fibrosis. The promise of these therapies will depend largely on effective delivery and engraftment. In this study, in the setting of human lung transplantation, we sought to determine whether exogenous epithelial cells are able to engraft the transplanted organ and if cells of a similar phenotype could be detected in peripheral blood.

Unified criteria for ultrasonographic diagnosis of ADPKD.

Individuals who are at risk for autosomal dominant polycystic kidney disease are often screened by ultrasound using diagnostic criteria derived from individuals with mutations in PKD1. Families with mutations in PKD2 typically have less severe disease, suggesting a potential need for different diagnostic criteria. In this study, 577 and 371 at-risk individuals from 58 PKD1 and 39 PKD2 families, respectively, were assessed by renal ultrasound and molecular genotyping.

MECP2 genomic structure and function: insights from ENCODE.

MECP2, a relatively small gene located in the human X chromosome, was initially described with three exons transcribing RNA from which the protein MeCP2 was translated. It is now known to have four exons from which two isoforms are translated; however, there is also evidence of additional functional genomic structures within MECP2, including exons potentially transcribing non-coding RNAs. Accompanying the recognition of a higher level of intricacy within MECP2 has been a recent surge of knowledge about the structure and function of human genes more generally, to the extent that the definition of a gene is being revisited.

Noncitrus fruits as novel dietary environmental modifiers of iron stores in people with or without HFE gene mutations.

Objective: To investigate whether citrus fruit, noncitrus fruit, and other dietary factors act as environmental modifiers of iron status in the absence or presence of hemochromatotic HFE gene mutations.

Participants And Methods: Iron studies, HFE genotypic analyses, and dietary data from a survey conducted from March 21, 1994, through December 15, 1995, were analyzed for a group of 2232 residents (1105 men, 1127 women) aged 20 to 79 years recruited from the community electoral roll of Busselton in Western Australia. Data were analyzed by linear regression analysis and analysis of covariance.

Directions for clinical practice improvement in HFE gene mutation testing.

Objective: To audit the clinical indications for HFE gene mutation testing in a consecutive series of requests.

Design: Retrospective audit of reasons prompting 187 HFE test requests received between June 2003 and June 2005, by examination of the request form, hospital notes (when available) and, when required, information from the referring doctor.

Setting: A tertiary care public teaching hospital laboratory, Perth, Western Australia.

The diagnosis of autism in a female: could it be Rett syndrome?

The overlap between autism and Rett syndrome clinical features has led to many cases of Rett syndrome being initially diagnosed with infantile autism or as having some autistic features. Both conditions seriously disrupt social and language development and are often accompanied by repetitive, nonpurposeful stereotypic hand movements. The aims of this study were to compare the early and subsequent clinical courses of female subjects with Rett syndrome categorised by whether or not a diagnosis of autism had been proposed before Rett syndrome had been diagnosed and compare the spectrum of methyl-CpG binding protein 2 (MECP2) mutations identified among the two groups.

Seizures in Rett syndrome: an overview from a one-year calendar study.

Background: Rett syndrome is a neurodevelopmental disorder mainly affecting females. It is principally caused by mutations in the MECP2 gene. Seizures occur in about 80% of subjects but there has been little research into the factors contributing to their frequency.

Recommendations of the 2006 Human Variome Project meeting.

Lists of variations in genomic DNA and their effects have been kept for some time and have been used in diagnostics and research. Although these lists have been carefully gathered and curated, there has been little standardization and coordination, complicating their use. Given the myriad possible variations in the estimated 24,000 genes in the human genome, it would be useful to have standard criteria for databases of variation.

PKDB: Polycystic Kidney Disease Mutation Database--a gene variant database for autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) arises from mutations in the PKD1 and PKD2 genes. The Polycystic Kidney Disease Mutation Database (PKDB) is an internet-accessible relational database containing comprehensive information about germline and somatic disease-causing variants within these two genes, as well as polymorphisms and variants of indeterminate pathogenicity. The PKDB database structure incorporates an interface between these gene variant data and any associated patient clinical data.

Predictors of seizure onset in Rett syndrome.

Objectives: To investigate risk factors for seizure onset in Rett syndrome.

Study Design: Information on presence and age at onset of seizures, perinatal and developmental history, and genetic status was abstracted on 275 cases in the Australian Rett Syndrome Database. Cox and Weibull regression were used to investigate and provide a model for predicting the effects of genetic and developmental factors on age at seizure onset.

Correlation between clinical severity in patients with Rett syndrome with a p.R168X or p.T158M MECP2 mutation, and the direction and degree of skewing of X-chromosome inactivation.

Introduction: Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder that is usually associated with mutations in the MECP2 gene. The most common mutations in the gene are p.R168X and p.

Rett syndrome in Australia: a review of the epidemiology.

Objective: To examine the prevalence, cumulative incidence, and survival in an Australian cohort with Rett syndrome (RTT).

Study Design: The Australian Rett Syndrome Database is a longitudinal data collection that included 276 verified female cases at the end of 2004. Survival was calculated using the Kaplan-Meier product limit method, and cumulative incidence was determined using the complement of the Kaplan-Meier method.

NTNG1 mutations are a rare cause of Rett syndrome.

A translocation that disrupted the netrin G1 gene (NTNG1) was recently reported in a patient with the early seizure variant of Rett syndrome (RTT). The netrin G1 protein (NTNG1) has an important role in the developing central nervous system, particularly in axonal guidance, signalling and NMDA receptor function and was a good candidate gene for RTT. We recruited 115 patients with RTT (females: 25 classic and 84 atypical; 6 males) but no mutation in the MECP2 gene.