Abstract
Background
Neu-Laxova syndrome (NLS) is a rare hereditary disorder featuring intrauterine growth retardation, remarkable oedema with skin restriction, limb contracture, ichthyosis, and craniofacial anomaly. NLS shares multiple overlapping characteristics with several other inheritable refractory diseases: for example, harlequin foetus and restrictive dermopathy. To date, many NLS patients have been described, although the number of NLS cases with clear genetic aetiology remains limited.
Objectives
To characterize the clinical and genetic features of NLS in two Chinese families.
Materials and Methods
Relevant skin tissue samples, blood specimens, and follow-up data from two unrelated Chinese families with perinatal fatal disorders were collected. To obtain a definitive diagnosis, six genes (ABCA12, LMNA, ZMPSTE24, PHGDH, PSAT1 and PSPH), previously implicated in the pathogenesis of inheritable refractory diseases with similar phenotypic expression to that of the affected members in the two pedigrees, were sequenced. We also performed tandem mass spectrometry, structural protein modelling, and immunohistochemical analysis to further support the genetic findings.
Results
New and recurrent missense mutations were identified in two genes (PHGDH and PSAT1) associated with NLS, which further supports the recent findings that NLS is genetically heterogeneous and could result from mutations in genes encoding enzymes of the L-serine biosynthesis pathway. Structural changes in PHGDH and PSAT1 proteins were revealed by molecular modelling. Finally, a tandem mass spectrometry assay and immunohistochemical analysis further corroborated the diagnosis of NLS.
Conclusion
This study is the first description of PHGDH and PSAT1 mutations in Chinese NLS patients, which strongly implicates them in the pathogenesis of NLS.
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Acknowledgements and disclosures
Acknowledgements: We thank the two families and all subjects for taking part in this study. We also thank the families for granting permission to publish this information. This work was supported by Nature Science Foundation of China (81472867), a grant from the Fund of Shanghai JiaoTong University School of Medicine (14XJ10029), and a grant from Fund of sailing project of Shanghai municipal science and technology commission (15YF1407700). Conflicts of interest: none.
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Ni, C., Cheng, RH., Zhang, J. et al. Novel and recurrent PHGDH and PSAT1 mutations in Chinese patients with Neu-Laxova syndrome. Eur J Dermatol 29, 641–646 (2019). https://doi.org/10.1684/ejd.2019.3673
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DOI: https://doi.org/10.1684/ejd.2019.3673