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Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants.

ABSTRACT: Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutations of SHP-2 have been found in children with myeloproliferative disorders or malignant leukemia, and some of these can affect brain development. In the present study, we aimed to identify and functionally characterize genetic variations in SHP-2 in 72 preterm and 58 full-term infants and to evaluate the effect of the variations on neurodevelopment in preterm infants. Twelve genetic variations were identified. Among them, two variations in the SHP-2 promoter, g.-317C?>?T and g.-273G?>?A, were found to significantly increase promoter activity, and the frequency of g.-273G?>?A was higher in preterm infants than in full-term infants. Two transcription factors, NF-?B and GABP?, were found to be involved in the transcriptional regulation of SHP-2 by the two above-mentioned variations. In particular, we found that g.-273G?>?A was significantly associated with delayed myelination and poor motor development in preterm infants. Our results suggest that a functional promoter variation in SHP-2 is associated with spontaneous preterm birth itself as well as white matter myelination and neurodevelopment.

SUBMITTER: Shim SY

PROVIDER: S-EPMC5519743 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants.

Shim So-Yeon SY Jeong Hye Jin HJ Park Hyo Jin HJ Kwon Eun Young EY Kim Bo Min BM Choi Yang Ji YJ Choi Youn-Hee YH Cho Su Jin SJ Choi Ji Ha JH Park Eun Ae EA

Scientific reports 20170720 1

Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutations of SHP-2 have been found in children with myeloproliferative disorders or malignant leukemia, and some of these can affect brain development. In the present study, we aimed to identify and functionally ch ...[more]

PMID: 28729690

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Project description:ObjectivesThe software "SyMRI" generates different MR contrasts and characterizes tissue properties based on a single acquisition of a multi-dynamic multi-echo (MDME)-FLAIR sequence. The aim of this study was to assess the applicability of "SyMRI" in the assessment of myelination in preterm and term-born neonates. Furthermore, "SyMRI" was compared with conventional MRI.MethodsA total of 30 preterm and term-born neonates were examined at term-equivalent age using a standardized MRI protocol. MDME sequence (acquisition time, 5 min, 24 s)-based post-processing was performed using "SyMRI". Myelination was assessed by scoring seven brain regions on quantitative T1-/T2-maps, generated by "SyMRI" and on standard T1-/T2-weighted images, acquired separately. Analysis of covariance (ANCOVA) (covariate, gestational age (GA) at MRI (GAMRI)) was used for group comparison.ResultsIn 25/30 patients (83.3%) (18 preterm and seven term-born neonates), "SyMRI" acquisitions were successfully performed. "SyMRI"-based myelination scores were significantly lower in preterm compared with term-born neonates (ANCOVA: T1: F(1, 22)?=?7.420, p?=?0.012; T2: F(1, 22)?=?5.658, p?=?0.026). "SyMRI"-based myelination scores positively correlated with GAMRI (T1: r?=?0.662, n?=?25, p???0.001; T2: r?=?0.676, n?=?25, p???0.001). The myelination scores based on standard MRI did not correlate with the GAMRI. No significant differences between preterm and term-born neonates were detectable.Conclusions"SyMRI" is a highly promising MR technique for neonatal brain imaging. "SyMRI" is superior to conventional MR sequences in the visual detection of delayed myelination in preterm neonates.Key points• By providing multiple MR contrasts, "SyMRI" is a time-saving method in neonatal brain imaging. • Differences concerning the myelination in term-born and preterm infants are visually detectable on T1-/T2-weighted maps generated by "SyMRI". • "SyMRI" allows a faster and more sensitive assessment of myelination compared with standard MR sequences.

Project description:Preterm birth survivors are at a higher risk of growth and developmental disabilities compared to their term counterparts. Development of strategies to lower the complications of preterm birth forms the rising need of the hour. Appropriate nutrition is essential for the growth and development of preterm infants. Early administration of optimal nutrition to preterm birth survivors lowers the risk of adverse health outcomes and improves cognition in adulthood. A group of neonatologists, pediatricians, and nutrition experts convened to discuss and frame evidence-based recommendations for optimizing nutrition in preterm low birth weight (LBW) infants. The following were the primary recommendations of the panel: (1) enteral feeding is safe and may be preferred to parenteral nutrition due to the complications associated with the latter; however, parenteral nutrition may be a useful adjunct to enteral feeding in some critical cases; (2) early, fast, or continuous enteral feeding yields better outcomes compared to late, slow, or intermittent feeding, respectively; (3) routine use of nasogastric tubes is not advisable; (4) preterm infants can be fed while on ventilator or continuous positive airway pressure; (5) routine evaluation of gastric residuals and abdominal girth should be avoided; (6) expressed breast milk (EBM) is the first choice for feeding preterm infants due to its beneficial effects on cardiovascular, neurological, bone health, and growth outcomes; the second choice is donor pasteurized human milk; (7) EBM or donor milk may be fortified with human milk fortifiers, without increasing the osmolality of the milk, to meet the high protein requirements of preterm infants; (8) standard fortification is effective and safe but does not fulfill the high protein needs; (9) use of targeted and adjustable fortification, where possible, helps provide optimal nutrition; (10) optimizing weight gain in preterm infants prevents long-term cardiovascular complications; (11) checking for optimal weight and sucking/swallowing ability is essential prior to discharge of preterm infants; and (12) appropriate counseling and regular follow-up and monitoring after discharge will help achieve better long-term health outcomes. This consensus summary serves as a useful guide to clinicians in addressing the challenges and providing optimal nutrition to preterm LBW infants.

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Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants.

Publications

Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants.

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