Background: Congenital hypothyroidism (CH) is defined as the lack of thyroid hormones at birth. Mutations in at least 15 different genes have been associated with this disease. While up to 20% of CH cases are hereditary, the majority of cases are sporadic with unknown etiology. Apart from a monogenic pattern of inheritance, multigenic mechanisms have been suggested to play a role in CH. The genetics of CH has not been studied in Finland so far. Therefore, multigenic sequencing of CH candidate genes was performed in a Finnish patient cohort with both familial and sporadic CH.Methods: A targeted next-generation sequencing (NGS) panel, covering all exons of the major CH genes, was applied for 15 patients with sporadic and 11 index cases with familial CH.Results: Among the familial cases, six pathogenic mutations were found in the TPO, PAX8, and TSHR genes. Furthermore, pathogenic NKX2.1 and TG mutations were identified from sporadic cases, together with likely pathogenic variants in the TG, NKX2.5, SLC26A4, and DUOX2 genes. All identified novel pathogenic mutations were confirmed by Sanger-sequencing and characterized in silico and/or in vitro.Conclusion: In summary, the CH panel provides an efficient, cost-effective, and multigenic screening tool for both known and novel CH gene mutations. Hence, it may be a useful method to identify accurately the genetic etiology for dyshormogenic, familial, or syndromic forms of CH.

BackgroundAlcohol is a well-known risk factor in unintentional drownings. Whereas psychotropic drugs, like alcohol, may cause psychomotor impairment and affect cognition, no detailed studies have focused on their association with drowning. Finland provides extensive post-mortem toxicological data for studies on drowning because of its high medico-legal autopsy rates.MethodsDrowning cases, 2000 through 2009, for which post-mortem toxicological analysis was performed, came from the database of the Toxicological Laboratory, Department of Forensic Medicine, University of Helsinki, using the ICD-10 nature-of-injury code T75.1. The data were narrowed to unintentional drowning, using the ICD-10 external-injury codes V90, V92, and W65–74. Each drowning case had its blood alcohol concentration (BAC) and concentrations of other drugs recorded. Evaluation of the contribution of psychotropic drugs to drowning was based on their blood concentration by means of a 6-grade scale.ResultsAmong victims ≥15 years old, unintentional drownings numbered 1697, of which, 303 (17.9%) were boating-related and 1394 (82.1%) non-boating-related. Among these, 65.0% of boating-related and 61.8% of non-boating-related victims were alcohol-positive (=BAC ≥ 50 mg/dL). The male-to-female ratio in alcohol-positive drownings was 7.3. At least one psychotropic drug appeared in 453 (26.7%) drowning cases, with some victims’ bodies showing up to 7 different drugs. Overall 70 different psychotropic drugs were detectable, with 134 (7.9%) cases both alcohol-negative and psychotropic-drug-positive, of these, 59 (3.5%) were graded 4 to 6, indicating a possible to very probable contribution to drowning. Our findings suggest that psychotropic drugs may play a significant role in drowning, in up to 14.5% of cases, independently or in association with alcohol.ConclusionsPsychotropic drugs alone or in association with alcohol may be an overlooked risk factor in drowning, due to their effects on psychomotor function and cognition. Future studies should also address other mechanisms—for instance drug-induced long-QT syndrome—by which drugs may contribute to drowning.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-017-4306-8) contains supplementary material, which is available to authorized users.

BackgroundPost-mortem (PM) ethanol production may hamper the interpretation of blood alcohol concentration (BAC) in victims of drowning. Different exclusion criteria (e.g. cases with low BAC or with protracted interval between death and toxicological analysis) have been proposed with no factual figures to reduce the potential bias due to PM ethanol production when examining the prevalence rates for alcohol-related drowning. The aim of this study is to verify the extent to which PM alcohol production may affect the accuracy of studies on drowning and alcohol.FindingsUnintentional fatal drowning cases (n = 967) for which a full medico-legal autopsy and toxicological analysis was performed, in Finland, from 2000 to 2013, and relevant variables (demographic data of the victims, month of incident, PM submersion time, blood alcohol concentration, urine alcohol concentration (UAC), vitreous humour alcohol concentration (VAC) were available. Overall, out of 967 unintentional drownings, 623 (64.4%) were positive for alcohol (BAC > 0 mg/dL), 595 (61.5%) had a BAC ≥ 50 mg/dL, and 567 (58.6%) a BAC ≥ 100 mg/dL. Simultaneous measurements, in each victim, of BAC, UAC, and VAC revealed PM ethanol production in only 4 victims (BAC: 25 mg/dL – 48 mg/dL). These false positive cases represented 0.4% of drownings with BAC > 0 mg/dL and 14.3% of drownings with BAC > 0 mg/dL and < 50 mg/dL.ConclusionsThe present study suggests that PM ethanol production has a limited impact on research addressing the prevalence rate for alcohol-related drowning and that the use of too rigorous exclusion criteria, such as those previously recommended, may led to a significant underestimation of actual alcohol-positive drowning cases.Electronic supplementary materialThe online version of this article (10.1186/s40621-018-0169-4) contains supplementary material, which is available to authorized users.

BackgroundAlcohol is a well-known risk factor in unintentional drownings. While psychotropic drugs may also cause psychomotor impairment and affect cognition, no detailed studies have focused on their association with drowning. Finland provides extensive post-mortem toxicological data for studies on drowning due to its high medico-legal autopsy rates.MethodsDrowning cases, 2000 through 2009, for which post-mortem toxicological analysis was performed, were selected from the database of Toxicological laboratory, Department of Forensic Medicine, University of Helsinki, using the ICD-10 nature of injury code T75.1. The data were narrowed down to unintentional drowning, using the ICD-10 external injury codes V90, V92 and W65–74. For each drowning case, the blood alcohol concentration (BAC) and the concentrations of other drugs were recorded. The contribution of psychotropic drugs to drowning was evaluated based on their blood concentration by mean of a 6-grade scale.ResultsAmong victims ≥ 15 years old, there were 1697 unintentional drownings. 303 (17.8%) were boating-related and 1394 (82.2%) non-boating-related. 65.0% of boating-related and 61.8% of non-boating-related victims were alcohol-positive (= BAC ≥ 0.5 ‰). The male to female ratio in alcohol-positive drownings was 7.3. At least one psychotropic drug was found in 453 (26.7%) drowning cases, with some victims having up to 7 different drugs. Overall 70 different psychotropic drugs were detected. 134 (7.9%) cases were both alcohol-negative and psychotropic drug -positive, of them 59 (3.5%) were graded 4 to 6, indicating possible to very probable contribution to drowning.ConclusionsPsychotropic drugs alone or in association with alcohol may be an overlooked risk factor to drowning due to their effects on psychomotor function and cognition. Future studies should also address other mechanisms, for instance drug-induced long QT-syndrome, by which drugs may contribute to drowning.