Sudden cardiac death due to deficiency of the mitochondrial inorganic pyrophosphatase PPA2

We have used whole exome sequencing to identify biallelic missense mutations in the nuclearencoded mitochondrial inorganic pyrophosphatase (PPA2) in ten individuals from four unrelated pedigrees that are associated with mitochondrial disease. These individuals show a range of severity, indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe symptoms include seizures, lactic acidosis and cardiac arrhythmia and death within days of birth. In the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life. Comparison of normal and mutated PPA2 containing mitochondria from fibroblasts showed the activity of inorganic pyrophosphatase significantly reduced in affected individuals. Recombinant PPA2 enzymes modeling hypomorphic missense mutations had decreased activity that correlated with disease severity. These findings confirm the pathogenicity of PPA2 mutations, and suggest that PPA2 is a new cardiomyopathy-associated protein, which has a greater physiological importance in mitochondrial function than previously recognized

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Prevalence and description of chronic daily headache in the general population in France

International audienceThe objective of this study was to describe the epidemiology, clinical presentation and consequences of chronic daily headache (CDH) in France. A representative nation-wide sample of the general population was identified using a stratified sampling method. Ten thousand five hundred and eight-five subjects were screened in face-to-face interviews, and data collected using a standard questionnaire. An overall point prevalence of CDH in the general population of 2.98% was observed. Two-thirds of these subjects presented migraine-like features. Severity, functional impact and healthcare consumption were higher than in subjects reporting episodic migraine in the same sample. Of the subjects, 28.2% reported the most severe migraine disability assessment scores (Grades 3 and 4), compared to 12% of episodic migraineurs. A qualité de vie et migraine score of 68.4 was observed, indicating severely attenuated quality of life. Only 6.6% of subjects were taking prophylactic treatment, whilst 88% were using non-specific acute headache treatments. The frequency of physician consultations and laboratory examinations was significantly higher than in individuals with episodic headache. CDH is thus a relatively prevalent condition in the general French population, associated with an important burden of suffering and with considerable expenditure in the health service. Management of this condition is generally inappropriate

Prevalence and description of chronic daily headache in the general population in France

International audienceThe objective of this study was to describe the epidemiology, clinical presentation and consequences of chronic daily headache (CDH) in France. A representative nation-wide sample of the general population was identified using a stratified sampling method. Ten thousand five hundred and eight-five subjects were screened in face-to-face interviews, and data collected using a standard questionnaire. An overall point prevalence of CDH in the general population of 2.98% was observed. Two-thirds of these subjects presented migraine-like features. Severity, functional impact and healthcare consumption were higher than in subjects reporting episodic migraine in the same sample. Of the subjects, 28.2% reported the most severe migraine disability assessment scores (Grades 3 and 4), compared to 12% of episodic migraineurs. A qualité de vie et migraine score of 68.4 was observed, indicating severely attenuated quality of life. Only 6.6% of subjects were taking prophylactic treatment, whilst 88% were using non-specific acute headache treatments. The frequency of physician consultations and laboratory examinations was significantly higher than in individuals with episodic headache. CDH is thus a relatively prevalent condition in the general French population, associated with an important burden of suffering and with considerable expenditure in the health service. Management of this condition is generally inappropriate

Assessment of the performances of AcuStar HIT and the combination with heparin-induced multiple electrode aggregometry: A retrospective study

Background: Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is challenging. HemosIL® AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) were recently proposed as rapid diagnostic methods. Objectives: We conducted a study to assess performances of AcuStar HIT-IgG (PF4-H) and AcuStar HIT-Ab (PF4-H). The secondary objective was to compare the performances of the combination of Acustar HIT and HIMEA with standardised clinical diagnosis. Methods: Sera of 104 suspected HIT patients were retrospectively tested with AcuStar HIT. HIMEA was performed on available sera (n = 81). The clinical diagnosis was established by analysing in a standardized manner the patient's medical records. These tests were also compared with PF4-Enhanced®, LTA, and SRA in subsets of patients. Thresholds were determined using ROC curve analysis with clinical outcome as reference. Results: Using the recommended thresholds (1.00 AU), the negative predictive value (NPV) of HIT-IgG and HIT-Ab were 100.0% (95% CI: 95.9%-100.0% and 95.7%-100.0%). The positive predictive value (PPV) were 64.3% (95% CI: 35.1%-87.2.2%) and 45.0% (95% CI: 23.2%-68.6%), respectively. Using our thresholds (HIT-IgG: 2.89 AU, HIT-Ab: 9.41 AU), NPV of HIT-IgG and HIT-Ab were 100.0% (95% CI: 96.0%-100.0% and 96.1%-100.0%). PPV were 75.0% (95% CI: 42.7%-94.5%) and 81.8% (95% CI: 48.3%-97.7%), respectively. Of the 79 patients with a medium-high pretest probability score, 67 were negative using HIT-IgG (PF4-H) test at our thresholds. HIMEA was performed on HIT-IgG positive patients. Using this combination, only one patient on 79 was incorrectly diagnosed. Conclusion: Acustar HIT showed good performances to exclude the diagnosis of HIT. Combination with HIMEA improves PPV. © 2013 Elsevier Ltd. All rights reserved