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1.  Missense dopamine transporter mutations associate with adult parkinsonism and ADHD 
The Journal of Clinical Investigation  2014;124(7):3107-3120.
Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls dopamine homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort of patients with atypical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with early-onset parkinsonism and ADHD. According to DAT single-photon emission computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG-PET/MRI) scan, the patient suffered from progressive dopaminergic neurodegeneration. In heterologous cells, both DAT variants exhibited markedly reduced dopamine uptake capacity but preserved membrane targeting, consistent with impaired catalytic activity. Computational simulations and uptake experiments suggested that the disrupted function of the DAT-Asp421Asn mutant is the result of compromised sodium binding, in agreement with Asp421 coordinating sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments revealed a constitutive, anomalous efflux of dopamine, and electrophysiological analyses identified a large cation leak that might further perturb dopaminergic neurotransmission. Our results link specific DAT missense mutations to neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies.
PMCID: PMC4071392  PMID: 24911152
2.  Severe and rapidly progressing cognitive phenotype in a SCA17-family with only marginally expanded CAG/CAA repeats in the TATA-box binding protein gene: A case report 
BMC Neurology  2012;12:73.
The autosomal dominant spinocerebellar ataxias (SCAs) confine a group of rare and heterogeneous disorders, which present with progressive ataxia and numerous other features e.g. peripheral neuropathy, macular degeneration and cognitive impairment, and a subset of these disorders is caused by CAG-repeat expansions in their respective genes. The diagnosing of the SCAs is often difficult due to the phenotypic overlap among several of the subtypes and with other neurodegenerative disorders e.g. Huntington’s disease.
Case presentation
We report a family in which the proband had rapidly progressing cognitive decline and only subtle cerebellar symptoms from age 42. Sequencing of the TATA-box binding protein gene revealed a modest elongation of the CAG/CAA-repeat of only two repeats above the non-pathogenic threshold of 41, confirming a diagnosis of SCA17. Normally, repeats within this range show reduced penetrance and result in a milder disease course with slower progression and later age of onset. Thus, this case presented with an unusual phenotype.
The current case highlights the diagnostic challenge of neurodegenerative disorders and the need for a thorough clinical and paraclinical examination of patients presenting with rapid cognitive decline to make a precise diagnosis on which further genetic counseling and initiation of treatment modalities can be based.
PMCID: PMC3475097  PMID: 22889412
Spinocerebellar ataxia type 17; Dementia; Short CAG repeat expansion
3.  Mortality and cancer morbidity among cadmium-exposed workers 
Preliminary data are reported from a study of 269 cadmium-nickel battery factory workers and 94 cadmium-copper alloy factory workers. The target group comprises all workers with more than 5 years exposure to cadmium at any time since the factories started production. An internal reference group of 328 alloy factory workers without cadmium exposure was also studied.
The expected number of deaths and cancers was calculated with the “life-table” method by using national average incidence rates for men in different age groups and at different calendar years.
It was found that among the workers in the battery factory who started work before 1948 there was an increased general mortality in the 1950's mainly due to respiratory disease. The same group had an increased renal disease mortality. There was no increase in general cancer mortality or in general cancer incidence. The risk ratio for nasopharyngeal cancer incidence was 10 (two cases), which was statistically significant. For some other sites like prostate, lung and colon-rectum the risk ratios were also greater than 1 but not statistically significant.
In the alloy factory there was a tendency for an increased mortality in prostatic cancer (four cases). After correction for the “healthy worker effect” using the reference group, the risk ratio for prostatic cancer deaths was calculated as 2.4, but this was not statistically significant. The findings in this study support the earlier reports of an association between human cadmium exposure and increased risk for prostatic cancer.
PMCID: PMC1637490  PMID: 488034
5.  Long-term respiratory symptoms following oesophageal atresia 
Acta Paediatrica (Oslo, Norway : 1992)  2011;100(9):1222-1225.
Oesophageal atresia (OA) is a congenital malformation that can lead to persistent respiratory symptoms in adulthood.
To describe the prevalence of respiratory symptoms in adulthood in a population-based study of patients with repaired OA and to compare this with the prevalence in the general population.
Of 80 patients operated for OA in Gothenburg in 1968–1983, 79 were located. The patients received a questionnaire on respiratory symptoms. Controls were 4979 gender- and age-matched subjects who answered the same questions.
The questionnaire was answered by 73 of 79 (92%) patients. Physician-diagnosed asthma was reported by 30% in the OA group vs 10% in the control group (OR 4.1; 95% CI 2.4–6.8), and recurrent wheeze in 29% vs 5.5% (OR 6.9; 4.1–11.6). Also wheeze during the last year, asthma medication, a long-standing cough, cough with sputum production and chronic bronchitis were significantly more common among the patients with OA. In contrast, there was no significant difference regarding risk factors for asthma. The prevalence of respiratory symptoms did not appear to decrease with age.
A high prevalence of respiratory symptoms remains among adult patients with repaired OA. Many of the patients had an asthma diagnosis. However, asthma heredity or allergic rhinitis was not overrepresented.
PMCID: PMC3187869  PMID: 21418293
Asthma; Oesophageal atresia; Outcome; Respiratory symptoms; Wheezing

Results 1-7 (7)