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Novel and recurrent PHGDH and PSAT1 mutations in Chinese patients with Neu-Laxova syndrome.
Eur J Dermatol. 2019 Dec 01; 29(6):641-646.EJ

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.

Authors+Show Affiliations

Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31903955

Citation

Ni, Cheng, et al. "Novel and Recurrent PHGDH and PSAT1 Mutations in Chinese Patients With Neu-Laxova Syndrome." European Journal of Dermatology : EJD, vol. 29, no. 6, 2019, pp. 641-646.
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. 2019;29(6):641-646.
Ni, C., Cheng, R. H., Zhang, J., Liang, J. Y., Wei, R. Q., Li, M., & Yao, Z. R. (2019). Novel and recurrent PHGDH and PSAT1 mutations in Chinese patients with Neu-Laxova syndrome. European Journal of Dermatology : EJD, 29(6), 641-646. https://doi.org/10.1684/ejd.2019.3673
Ni C, et al. Novel and Recurrent PHGDH and PSAT1 Mutations in Chinese Patients With Neu-Laxova Syndrome. Eur J Dermatol. 2019 Dec 1;29(6):641-646. PubMed PMID: 31903955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel and recurrent PHGDH and PSAT1 mutations in Chinese patients with Neu-Laxova syndrome. AU - Ni,Cheng, AU - Cheng,Ru-Hong, AU - Zhang,Jia, AU - Liang,Jian-Ying, AU - Wei,Ru-Qu, AU - Li,Ming, AU - Yao,Zhi-Rong, PY - 2020/1/7/entrez PY - 2020/1/7/pubmed PY - 2020/6/12/medline KW - Neu-Laxova syndrome KW - PHGDH KW - PSAT1 KW - genetic heterogeneity KW - phenotypic heterogeneity SP - 641 EP - 646 JF - European journal of dermatology : EJD JO - Eur J Dermatol VL - 29 IS - 6 N2 - 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. SN - 1952-4013 UR - https://www.unboundmedicine.com/medline/citation/31903955/Novel_and_recurrent_PHGDH_and_PSAT1_mutations_in_Chinese_patients_with_Neu_Laxova_syndrome_ L2 - http://www.john-libbey-eurotext.fr/medline.md?doi=10.1684/ejd.2019.3673 DB - PRIME DP - Unbound Medicine ER -