The V599E-IGF1R mutation interferes with the receptor's trafficking path, thereby abrogating proreceptor processing and plasma membrane localization. Diminished cell surface receptor density solely expressed from the patient's wild-type allele is supposed to lead to insufficient IGF-I signaling. We hypothesize that this mechanism results in intrauterine and postnatal growth retardation of the affected patient. The reported retention of the nascent IGF1R in the endoplasmic reticulum presents a novel mechanism of IGF-I resistance.

The identified G1125A mutation results in a kinase-deficient IGF1R, which is likely to cause the phenotype of intrauterine and postnatal growth retardation.

The results that follow prove the fundamental feasibility of an NC drill for surgery of the petrosal bone using the example of the simple mastoidectomy in the laboratory test. When using NC, tissue resection is faster, more precise, and has fewer related complications than the same procedure without. The results offer a very promising basis for the introduction of a newly conceived system to the procedure of NC surgery on the petrosal bone. The device configuration used here was originally conceived for NC guidance of a shaver in functional endoscopic sinus surgery. Individual errors will have to be mitigated through the new version of the control unit presently in development.

Anxiety and depressive symptoms have adverse effects on children's development. The present study investigates the associations of socioeconomic factors as well as maternal emotional health with children's emotional health status. The data were collected between 2011 and 2015 in the LIFE Child study, a population-based cohort study in Leipzig, Germany. The emotional health status of 1093 children (2.5-11.9 years old) was investigated using the subscale 'emotional problems' of the Strengths and Difficulties Questionnaire. Associations of maternal emotional health, family status, and socioeconomic status (SES) with the emotional health status of children were estimated via regression analyses. 21.13% of the participating children were assigned to the 'risk' group for emotional problems. The results furthermore revealed that children of mothers reporting more depressive symptoms, children living in single-parent families, and children of families with lower SES scored higher in the emotional problems scale. When considering the different indicators of SES (parental education, occupational status, and monthly net income) separately, only income showed significant associations with children's emotional health status. The prevalence of emotional problems in children in Leipzig, a city in East Germany, appears to be higher than the previously reported German average. Maternal depressive symptoms, single-parent families, lower SES, and especially lower income can be seen as risk factors for children's emotional health.

This study examined the role of structural and content characteristics of children's conflict-based narratives (coherence, positive and aggressive themes) in the association between early childhood family risk and children's internalizing and externalizing problems in a sample of 193 children (97 girls, 96 boys) aged 3 to 5 years (M = 3.85, SD = .48). Parents participated in an interview on family related risk factors; teachers and parents completed the Strengths and Difficulties Questionnaire; children completed conflict-based narratives based on the MacArthur Story Stem Battery (MSSB). We specifically investigated the mediating and moderating role of narrative coherence and content themes in the association between family risk and children's internalizing and externalizing problems. Children's narrative coherence was associated with better adjustment, and had a buffering effect on the negative relation between family risk on children's internalizing problems. Positive themes were negatively associated with externalizing problems. Telling narratives with many positive and negative themes buffered the negative association of family risk and teacher-reported externalizing problems. In sum, the findings suggest that in children, being able to tell coherent and enriched narratives may buffer the impact of family risk on their symptoms, and being able to produce positive themes rather than aggressive themes is associated with lower externalizing problems.

BackgroundThis study aims to establish age- and gender-specific cystatin C (CysC) reference values for healthy infants, children, and adolescents and to relate them to pubertal stage, height, weight, and body mass index (BMI).MethodsSerum CysC and creatinine levels of 6217 fasting, morning venous blood samples from 2803 healthy participants of the LIFE Child study (age 3 months to 18 years) were analyzed by an immunoassay. Recruitment started in 2011; 1636 participants provided at least one follow-up measurement. Percentiles for CysC were calculated. Age- and gender-related effects of height, weight, BMI, and puberty status were assessed through linear regression models.ResultsOver the first 2 years of life, median CysC levels decrease depending on height (ß = − 0.010 mg/l/cm, p < 0.001) and weight (ß = − 0.033 mg/l/kg, p < 0.001) from 1.06 to 0.88 mg/l for males and from 1.04 to 0.87 mg/l for females. Following the second year of age, the levels remain stable for eight years. From 11 to 14 years of age, there is an increase of median CysC levels in males to 0.98 mg/l and a decrease in females to 0.86 mg/l. The change is associated with puberty (ß = 0.105 mg/l/Tanner stage, p < 0.001 in males and ß = − 0.093 mg/l/Tanner stage, p < 0.01 in females) and in males with height (ß = 0.003 mg/l/cm, p < 0.001).ConclusionsCysC levels depend on age, gender, and height, especially during infancy and puberty. We recommend the use of age- and gender-specific reference values for CysC serum levels for estimating kidney function in clinical practice.Electronic supplementary materialThe online version of this article (10.1007/s00467-018-4087-z) contains supplementary material, which is available to authorized users.

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Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA) with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X]) were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration.