Prenatal and early diagnosis of Chinese 3-M syndrome patients with novel pathogenic variants

Abstract

Background: 3-M syndrome is a clinically recognizable yet under-diagnosed primordial growth retardation disorder. Molecular testing for CUL7, OBSL1 or CCDC8 genes can provide confirmed diagnosis for patients at prenatal or early age. So far, the clinical and molecular features of Chinese 3-M syndrome patients have not been reported.

Methods: In this article, the authors performed prenatal and early diagnosis of Chinese patients with 3-M syndrome by Next-Generation Sequencing.

Results: The authors reported six unrelated Chinese 3-M syndrome patients. Five of the six patients were diagnosed before two years of age including one prenatal case. The authors identified six novel pathogenic variants and five previously reported pathogenic variants. The authors' clinical evaluations indicated that Chinese 3-M syndrome patients share similar recognizable features as those reported in patients of other ethnic background. The authors noticed some uncommon features in this small cohort of Chinese patients such as delayed motor development at early ages, undelayed bone age and presence of lower eyelid fat pads.

Conclusion: The authors' study of Chinese 3-M syndrome patients revealed novel mutations and clinical phenotypes.

Keywords: 3-M syndrome; Bone age; CUL7; Chinese cohort; OBSL1; Short stature.