Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder.

TIMMDC1 encodes the Translocase of Inner Mitochondrial Membrane Domain-Containing protein 1 (TIMMDC1) subunit of complex I of the electron transport chain responsible for ATP production. We studied a consanguineous family with two affected children, now deceased, who presented with failure to thrive in the early postnatal period, poor feeding, hypotonia, peripheral neuropathy and drug-resistant epilepsy. Genome sequencing data revealed a known, deep intronic pathogenic variant TIMMDC1 c.

Marfan syndrome resulting from a rare pathogenic FBN1 variant, ascertained through a proband with IgG4-related arteriopathy.

A 57-year-old man with a family history of aortic aneurysm was found, during assessment of unexplained fever, to have an infrarenal aortic aneurysm requiring immediate repair. Dilatation of popliteal and iliac arteries was also present. Progressive aortic root dilatation with aortic regurgitation was documented from 70 years leading to valve-sparing aortic root replacement at 77 years, at which time genetic studies identified a likely pathogenic FBN1 missense variant c.

Single-nucleotide polymorphism associations with preterm delivery: a case-control replication study and meta-analysis.

Background: The aim of this study was to replicate single-nucleotide polymorphism (SNP) associations with preterm birth (PTB; birth at <37 completed weeks of gestation) and synthesize currently available evidence using meta-analysis.

Methods: Spontaneous PTB cases and controls were selected from an existing cohort. Candidate SNPs were taken from an existing genotype panel.

Genetic and clinical contributions to cerebral palsy: a multi-variable analysis.

Aim: This study aims to examine single nucleotide polymorphism (SNP) associations with cerebral palsy in a multi-variable analysis adjusting for potential clinical confounders and to assess SNP-SNP and SNP-maternal infection interactions as contributors to cerebral palsy.

Methods: A case control study including 587 children with cerebral palsy and 1154 control children without cerebral palsy. Thirty-nine candidate SNPs were genotyped in both mother and child.

Reproductive technologies and the risk of birth defects.

Background: The extent to which birth defects after infertility treatment may be explained by underlying parental factors is uncertain.

Methods: We linked a census of treatment with assisted reproductive technology in South Australia to a registry of births and terminations with a gestation period of at least 20 weeks or a birth weight of at least 400 g and registries of birth defects (including cerebral palsy and terminations for defects at any gestational period). We compared risks of birth defects (diagnosed before a child's fifth birthday) among pregnancies in women who received treatment with assisted reproductive technology, spontaneous pregnancies (i.

Epidemiologic associations with cerebral palsy.

Objective: To estimate epidemiologic risk factors for cerebral palsy.

Methods: Data were collected by linkage to state-based perinatal repositories and cerebral palsy registers and using a maternal questionnaire. The cohort included 587 individuals with cerebral palsy and 1,154 non-cerebral palsy controls.

A new syndrome with craniosynostosis and cleft lip and palate.

Two unrelated girls with craniosynostosis and bilateral cleft lip and palate who also had developmental delay and umbilical herniae are presented. We propose that these patients have the same condition, and that their combination of features may constitute a new syndrome. Management of the patients is discussed.

Fetal MBL2 haplotypes combined with viral exposure are associated with adverse pregnancy outcomes.

Objective: To investigate the roles of inherited polymorphisms in the MBL2 gene and exposure to viral infection in the development of a range of adverse pregnancy outcomes, including birthweight  < 10th percentile (small-for-gestational age, SGA), antepartum hemorrhage (APH), pregnancy-induced hypertensive disorders (PIHD), and preterm birth (PTB).

Methods: This was a case-control study using DNA from newborn screening cards of 717 cases (babies with at least one of the adverse pregnancy outcomes listed above) and 609 controls, to screen for six polymorphisms within the MBL2 gene. These combine to create haplotypes with high (HYPA), intermediate (LYQA, LYPA), low (LXPA), and defective (HYPD, LYQC, LYPB) circulating MBL2 levels.

The Australian cerebral palsy research study--protocol for a national collaborative study investigating genomic and clinical associations with cerebral palsy.

Aim: Previous studies have proposed a link between the presence of specific single nucleotide polymorphisms (SNPs) and cerebral palsy and the majority of these associations remain to be confirmed or rejected by prospective studies with sufficient statistical power. Prior studies have also given little attention to the interaction of genomic characteristics and clinical risk factors.

Methods: This paper describes the design of a prospective case-control study to test these genetic associations in conjunction with more stringent data collection in respect to clinical features associated with pregnancy, particularly maternal infection.

CP or not CP? A review of diagnoses in a cerebral palsy register.

The purpose of this study was to document the inaccuracy rate of diagnosis of cerebral palsy recorded on the South Australian Cerebral Palsy Register. A total of 402 children born in South Australia from 1993 to 2002 and notified to the Register as having cerebral palsy were identified through the Register database, and 21 children (5.2%) were later identified to have a noncerebral palsy diagnosis.

DNA from buccal swabs suitable for high-throughput SNP multiplex analysis.

We sought a convenient and reliable method for collection of genetic material that is inexpensive and noninvasive and suitable for self-collection and mailing and a compatible, commercial DNA extraction protocol to meet quantitative and qualitative requirements for high-throughput single nucleotide polymorphism (SNP) multiplex analysis on an automated platform. Buccal swabs were collected from 34 individuals as part of a pilot study to test commercially available buccal swabs and DNA extraction kits. DNA was quantified on a spectrofluorometer with Picogreen dsDNA prior to testing the DNA integrity with predesigned SNP multiplex assays.

Genetic susceptibility to viral exposure may increase the risk of cerebral palsy.

Aim: Cytokine polymorphisms may alter the fetal inflammatory response, increasing susceptibility to cerebral palsy (CP). This study investigates associations between selected inflammatory mediator and cytokine gene polymorphisms (Toll-like receptor-4 (TLR-4) Asp299Gly, interleukin-6 G-174C and interleukin-4 C-589T) and CP from 443 CP infants and 883 control infants. Results were correlated with viral nucleic acids in the same samples.

Folate awareness and the prevalence of neural tube defects in South Australia, 1966-2007.

Objectives: To ascertain changes in: women's knowledge of the role of folic acid in the prevention of neural tube defects (NTDs); intake of folic acid among pregnant women; and prevalence of NTDs in South Australia.

Design, Setting And Participants: Computer-assisted telephone interviews of South Australian households from 1994 to 2007 over a period encompassing a statewide folate promotion campaign (1994-1995), continuing folate promotion, as well as the introduction of voluntary folate fortification of foods (1996); ascertainment of the total prevalence of NTDs from births and terminations of pregnancy from 1966 to 2007.

Main Outcome Measures: Changes in women's knowledge of the role of folic acid in the prevention of NTDs; changes in the prevalence of NTDs.

Association between Apolipoprotein E genotype and cerebral palsy is not confirmed in a Caucasian population.

Apolipoprotein E (APOE) plays a significant role in lipid metabolism and has been implicated in the growth and repair of injured neurons. Two small studies have suggested an association between APOE genotype and cerebral palsy. We investigated if APOE genotype is associated with an increased risk for cerebral palsy, influences the type of cerebral palsy or interacts with prenatal viral infection to influence risk of cerebral palsy.

Self-esteem, self-concept, and quality of life in children with hemiplegic cerebral palsy.

Objectives: To investigate self-esteem, self-concept and quality of life in children with hemiplegic cerebral palsy (HCP) compared with typically developing peers.

Study Design: Cross-sectional evaluation of 86 children (3-16 years; 54 boys; mean age 9.4 +/- 3.

Mannose-binding lectin haplotypes may be associated with cerebral palsy only after perinatal viral exposure.

Objective: The objective of the study was to investigate the associations between infection, polymorphisms in the mannose-binding lectin gene (MBL), and cerebral palsy (CP).

Study Design: This was a case-control study using deoxyribonucleic acid from newborn screening cards of 443 Caucasian CP cases and 883 Caucasian controls to screen for 6 polymorphisms within the MBL gene. These polymorphisms combine to create haplotypes with high (HYPA), intermediate (LYQA, LYPA), low (LXPA), and defective (HYPD, LYQC, LYPB) circulating MBL levels.

Trends in state/population-based Down syndrome screening and invasive prenatal testing with the introduction of first-trimester combined Down syndrome screening, South Australia, 1995-2005.

Objective: The purpose of this study was to review trends in the us of maternal serum Down syndrome screening and invasive prenatal testing before and after the introduction of a state-based first-trimester combined Down syndrome screening program.

Study Design: A retrospective population-based study was performed on first- and second-trimester Down syndrome screening, invasive prenatal testing, and prenatal detection of Down syndrome from 1995 to 2005 in South Australia with data from state-based registers. Chi-square tests were used to evaluate trends.

Associations between fetal inherited thrombophilia and adverse pregnancy outcomes.

Objective: The purpose of this study was to investigate associations between fetal inherited thrombophilia and adverse pregnancy outcomes, including pregnancy-induced hypertensive disorders (PIHD), antepartum hemorrhage (APH), small-for-gestational age <10th percentile (SGA), and preterm birth (PTB).

Study Design: Seven hundred and seventeen cases and 609 controls were genotyped for Factor V Leiden (FVL, G1691A), Prothrombin gene mutation (PGM, G20210A), and Methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C using DNA from newborn screening cards.

Results: For babies born <28 weeks' gestation, PGM was associated with an increased risk of SGA (OR 6.

The association between inherited cytokine polymorphisms and cerebral palsy.

Objective: The purpose of this study was to investigate associations between inherited cytokine polymorphisms and cerebral palsy.

Study Design: This was a case-control study that used DNA from the newborn infant screening cards of 443 white infants with cerebral palsy and 883 white control infants to test for the following cytokine polymorphisms: tumor necrosis factor-alpha-308, mannose-binding lectin-221, and 3 polymorphisms in exon-1 of the mannose-binding lectin gene at codon-52, -54, and -57.

Results: At all gestational ages mannose-binding lectin codon-54 increased the risk of the development of diplegia (homozygous or heterozygous odds ratio, 1.

Neurotropic viruses and cerebral palsy: population based case-control study.

Objective: To investigate the association between cerebral palsy and direct evidence for perinatal exposure to neurotropic viruses.

Design: Population based case-control study.

Setting: Adelaide Women's and Children's Hospital Research Laboratory.

Associations between inherited thrombophilias, gestational age, and cerebral palsy.

Objective: This study was undertaken to investigate associations between inherited thrombophilic polymorphisms and cerebral palsy (CP) in a large case-control study.

Study Design: This is a population-based case-control study. Genomic DNA from newborn screening cards of 443 white CP cases and 883 white controls was tested for factor V Leiden (FVL, G1691A), prothrombin gene mutation (PGM, G20210A), and methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C.

The prevalence of inherited thrombophilias in a Caucasian Australian population.

Aims: To describe the prevalence of four inherited thrombophilias and their combinations for the first time in a large Caucasian Australian population.

Methods: Newborn screening cards of 883 Caucasian babies born in South Australia in 1986-1999 were de-identified and tested for the following inherited thrombophilic polymorphisms: factor V Leiden (G1691A), prothrombin gene mutation (G20210A), methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C, as well as compound heterozygosity for the MTHFR polymorphisms.

Results: The birth prevalences of heterozygosity and homozygosity for the four thrombophilic polymorphisms were: factor V Leiden 9.