Novel CUL7 biallelic mutations alter the skeletal phenotype of 3M syndrome

Nao Takizaki,Hiroshi Ishikawa,Yumi Enomoto,Noriko Aida,Hiroaki Murakami,Gen Nishimura,Yoshinori Tsurusaki,Kenji Kurosawa,Koji Muroya,Kaoru Katsumata

doi:10.1038/s41439-020-0090-6

Abstract

3M syndrome is an autosomal recessive disorder characterized by severe growth retardation, distinct facial features, and skeletal changes, including long slender tubular bones and tall vertebral bodies. We report a Japanese patient with 3M syndrome caused by the biallelic novel variants c.1705_1708del and c.1989_1999del of CUL7. Skeletal features were consistent with 3M syndrome in the early neonatal period but became less obvious by 2 years of age.

Highlights

3M syndrome is an autosomal recessive disorder characterized by severe growth retardation, distinct facial features, and skeletal changes, including long slender tubular bones and tall vertebral bodies
At 1 year and 3 months, reevaluation of skeletal X-rays showed mild manifestations for typical 3M syndrome compared with those observed at birth (Fig. 1e, f)
We identified the compound heterozygous variants NM_014780.4:c.1705_1708del:p.(Gly569Leufs*4) and c.1989_1999del:p.(Gln664Glyfs*12) of CUL7

Summary

Introduction

We report a patient with novel compound heterozygous mutations who developed less-severe distinct skeletal features during the neonatal period until 2 years of age. At 1 year and 3 months, reevaluation of skeletal X-rays showed mild manifestations for typical 3M syndrome compared with those observed at birth (Fig. 1e, f). At the age of 1 year and 10 months, his weight was 6180 g (−4.3 SD), length was 62.8 cm (−7.3 SD), occipital frontal circumference was 46.5 cm (−1.1 SD), and chest circumference was 31.4 cm (Fig. 1g).

Results

Conclusion