The Cardiac Phenotype in Patients With a CHD7 Mutation

Background- Loss-of-function mutations in CHD7 cause Coloboma, Heart Disease, Atresia of Choanae, Retardation of Growth and/or Development, Genital Hypoplasia, and Ear Abnormalities With or Without Deafness (CHARGE) syndrome, a variable combination of multiple congenital malformations including heart defects. Heart defects are reported in 70% to 92% of patients with a CHD7 mutation, but most studies are small and do not provide a detailed classification of the defects. We present the first, detailed, descriptive study on the cardiac phenotype of 299 patients with a CHD7 mutation and discuss the role of CHD7 in cardiac development. Methods and Results- We collected information on congenital heart defects in 299 patients with a pathogenic CHD7 mutation, of whom 220 (74%) had a congenital heart defect. Detailed information on the heart defects was available for 202 of these patients. We classified the heart defects based on embryonic cardiac development and compared the distribution to 1007 equally classified nonsyndromic heart defects of patients registered by EUROCAT, a European Registry of Congenital Anomalies. Heart defe Conclusions- CHD7 plays an important role in cardiac development, given that we found a wide range of heart defects in 74% of a large cohort of patients with a CHD7 mutation. Conotruncal defects and atrioventricular septal defects are over-represented in patients with CHD7 mutations compared with patients with nonsyndromic heart defects

Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome

In 2016, we described that missense variants in parts of exons 30 and 31 of CREBBP can cause a phenotype that differs from Rubinstein-Taybi syndrome (RSTS). Here we report on another 11 patients with variants in this region of CREBBP (between bp 5,128 and 5,614) and two with variants in the homologous region of EP300. None of the patients show characteristics typical for RSTS. The variants were detected by exome sequencing using a panel for intellectual disability in all but one individual, in whom Sanger sequencing was performed upon clinical recognition of the entity. The main characteristics of the patients are developmental delay (90%), autistic behavior (65%), short stature (42%), and microcephaly (43%). Medical problems include feeding problems (75%), vision (50%), and hearing (54%) impairments, recurrent upper airway infections (42%), and epilepsy (21%). Major malformations are less common except for cryptorchidism (46% of males), and cerebral anomalies (70%). Individuals with variants between bp 5,595 and 5,614 of CREBBP show a specific phenotype (ptosis, telecanthi, short and upslanted palpebral fissures, depressed nasal ridge, short nose, anteverted nares, short columella, and long philtrum). 3D face shape demonstrated resemblance to individuals with a duplication of 16p13.3 (the region that includes CREBBP), possibly indicating a gain of function. The other affected individuals show a less specific phenotype. We conclude that there is now more firm evidence that variants in these specific regions of CREBBP and EP300 result in a phenotype that differs from RSTS, and that this phenotype may be heterogeneous

Causes and consequences of personal financial management in the case of larger and structural charitable donations

We study causes and consequences of financial management in households in the specific case of charitable giving. We test hypotheses using couples in the Giving in the Netherlands Panel Study (n = 1,101). We find that more relationship specific investments lead to deciding on charitable giving as one economic actor. Furthermore, we find that the partner with the highest relative educational resources has most decision making power over charitable donations. Separately deciding couples are smallest charitable donors. Households in which the male partner decides are largest charitable donors when only larger and more structural donations are considered. This can be explained by their more conservative religious denomination. Re´sume´ Notre e´tude porte sur les causes et les conse´quences de la gestion financie`re des me´nages pour le cas spe´cifique des dons caritatifs. Nous testons des hypothe`ses a` travers un panel de quelques couples des Pays-Bas (GINPS) en matie`re de dons (n = 1,101). Nous trouvons que davantage d’investissements spe´cifiques relationnels conduisent a` prendre en compte le don caritatif en tant qu’acteur e´conomique. En outre, nous trouvons que le conjoint au revenu le plus e´leve´ de´tient le plus de pouvoir de´cisionnel quand il s’agit de faire des dons de charite´. Les couples qui prennent les de´cisions se´pare´ment sont les donateurs les plus modestes. Lorsque des dons structurels importants sont envisage´s, les me´nages dans lesquels l’homme prend les de´cisions sont les donateurs les plus ge´ne´reux. Une confession religieuse conservatrice peut venir expliquer cette conduite Zusammenfassung Wir untersuchen Gru¨nde und Folgen der Verwaltung der Haushaltsfinanzen speziell bezogen auf das Spenden fu¨ r wohlta¨tige Zwecke. Wir testen Hypothesen an Paaren im Projekt Giving in the Netherlands Panel Study (n = 1,101). Wir finden, dass Paare bei beziehungsspezifischeren Investitionen eine Spendenentscheidung als eine o¨konomische Einheit treffen. Außerdem entdecken wir, dass der Partner mit dem ho¨chsten relativen Bildungsniveau die gro¨ßere Entscheidungsbefugnis u¨ber wohlta¨tiges Spenden hat. Paare, wo Partner separat entscheiden, spenden am wenigsten. Haushalte, in denen der ma¨nnliche Partner entscheidet, sind die gro¨ßten Spender bei gro¨ßeren und strukturelleren Spenden. Dies kann mit deren Zugeho¨rigkeit zu konservativeren Glaubensgemeinschaften erkla¨rt werden. Resumen Hemos estudiado las causas y las consecuencias de la administracio´n econo´mica de los hogares en el caso especı´fico de las donaciones caritativas. Probamos diversas hipo´tesis con parejas dentro del Estudio del Panel de las Donaciones en los Paı´ses Bajos (n = 1,101). El resultado es que las inversiones especı´ficas de relacio´n llevan a decidir sobre las donaciones caritativas como un actor econo´mico. Asimismo, hemos descubierto que el co´nyuge con ma´s recursos educativos tiene ma´s poder de decisio´n sobre las donaciones caritativas. Las parejas que deciden por separado son donantes de menor envergadura, mientras que los hogares en los que decide el co´nyuge masculino son donantes de ma´s envergadura, solo cuando se tienen en cuenta ma´s y mayores donativos estructurales. Esto puede explicarse por su cara´cter religioso ma´s conservador.