A homozygous mutation in the highly conserved Tyr60 of the mature IGF1 peptide broadens the spectrum of IGF1 deficiency

Walenkamp, M.J.E.; Wit, J. M.

doi:10.1530/eje-19-0801

Cited by 3 publications

(2 citation statements)

References 46 publications

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“…Patients with genetic IGF-1R defects, show symptoms (i.e., pre and postnatal growth retardation, microcephaly, cardiac defects and dysmorphic features) that significantly overlap with those presented in various CDG types [ 19 , 20 ]. For example, the majority of CDG patients analyzed in the present study showed growth failure and microcephaly (Supplementary Table 1), which are also clinical hallmarks of IGF-1/IGF-1R defects [ 36 – 38 ]. Further studies are needed, also taking advantage of the recently developed CDG animal models [ 28 ], to evaluate the impact of glycosylation defects on each component of the IGF-1 system.…”

Section: Discussionmentioning

confidence: 99%

Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation

Patria

Annibalini

Morrone

et al. 2022

Cell. Mol. Life Sci.

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The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. ER-stress-related gene expression negatively correlated with fibroblasts IGF-1 secretion. This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG.

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Section: Discussionmentioning

confidence: 99%

Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation

Patria

Annibalini

Morrone

et al. 2022

Cell. Mol. Life Sci.

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“…GH de ciency/insensitivity and IGF1 de ciency play an important role in intrauterine linear and cranial growth [50]. The primary clinical features of a homozygous de cient IGF1 include perinatal growth restriction, severe microcephaly as well as severe global developmental delay [51].…”

Section: Discussionmentioning

confidence: 99%

Association of prenatal depression and plasma prolactin concentrations with neonatal birthweight

Wang

Jia

Zhang

et al. 2022

Preprint

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Background: Accumulating evidence suggests that prenatal depression is associated with altered birthweight in the offspring. The hormone prolactin (PRL) plays an important role in the etiology of mood disorders in women, especially for depression. We tested the hypotheses that maternal prenatal PRL levels can significantly influence neonatal birthweight and adequate PRL levels can alleviate prenatal depression-induced normal neonatal birthweight loss risk. Methods: The study population consisted of 392 mother-infant dyads. Symptoms of maternal prenatal depression were evaluated through the Edinburgh Postnatal Depression Scale and concentrations of plasma PRL and placental growth hormone (PGH) were measured before the delivery and umbilical cord plasma levels of insulin-like growth factor -1(IGF1) were measured at birth. The associations among maternal depressed symptoms, concentrations of related hormones and infant's birthweight were examined through linear regressions models. Results: Infants of low maternal PRL had a 0.169 unit (95%CI, -0.488,- 0.130) decrease in the birthweight Z-score compared to infants whose mothers had adequate PRL. Infants of depressed mothers with low PRL had a 0.253 unit(95%CI, -0.853,-0.369) decrease in the birthweight Z score compared to infants whose mothers had adequate PRL and normal emotion. Among infants of depressed mothers, we demonstrated that neonatal birthweight was reduced by a 0.285 unit if the mothers had low PRL concentrations compared to adequate PRL concentrations. As compared with low maternal PRL concentrations, high PRL concentrations were associated with an increase in the concentrations of IGF1 in offspring, but no association with PGH.Conclusion: We found that prenatal depression and low maternal PRL levels are at increased risk of normal infant’ s birthweight loss as measured by weight Z-score and sufficient maternal PRL levels would mitigate the adverse impact of prenatal depression on birthweight. We also found that prenatal depression and low PRL concentrations were associated with reduced fetal IGF1.

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Disorders of IGFs and IGF-1R signaling pathways

Forbes

Blyth

Wit

2020

Molecular and Cellular Endocrinology

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A homozygous mutation in the highly conserved Tyr60 of the mature IGF1 peptide broadens the spectrum of IGF1 deficiency

Cited by 3 publications

References 46 publications

Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation

Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation

Association of prenatal depression and plasma prolactin concentrations with neonatal birthweight

Disorders of IGFs and IGF-1R signaling pathways

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