3M syndrome is characterized by severe pre- and postnatal growth retardation, typical facial features, and normal intelligence. Homozygous or compound heterozygous mutations in either CUL7, OBSL1, or CCDC8 have been identified in the etiology so far. Clinical and molecular features of 24 patients (23 patients and a fetus) from 19 unrelated families with a clinical diagnosis of 3M syndrome were evaluated and genotype-phenotype correlations were investigated with the use of DNA sequencing, chromosomal microarray, and whole exome sequencing accordingly. A genetic etiology could be established in 20 patients (n = 20/24, 83%). Eleven distinct CUL7 or OBSL1 mutations, among which eight was novel, were identified in 18 patients (n = 18/24, 75%). Ten patients had CUL7 (n = 10/18, 56%) while eight had OBSL1 (n = 8/18, 44%) mutations. Birth weight and height standard deviation scores at admission were significantly (p < 0.05) lower in patients with CUL7 mutation compared to that of patients with OBSL1 mutation. Two patients with a similar phenotype had a de novo 20p13p deletion involving BMP2. No genetic etiology could be established in four patients (n = 4/28, 17%). This study yet represents the largest cohort of 3M syndrome patients from a single center in Turkey. Microdeletions involving BMP2 may cause a phenotype similar to 3M syndrome with some distinctive features. Larger cohort of patients are required to establish genotype-phenotype correlations in 3M syndrome.
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Clinical and molecular spectrum along with genotype-phenotype correlation of 25 patients diagnosed with 3 M syndrome: a study from Turkey.
Eur J Pediatr
December 2024
Department of Pediatric Genetics, Faculty of Medicine, Marmara University, Istanbul, Turkey.
Unlabelled: 3 M syndrome is a well-known autosomal recessive skeletal genetic disorder caused by biallelic pathogenic variants in the CUL7, OBSL1, and CCDC8 genes. Affected individuals exhibit profound pre- and postnatal growth retardation, distinctive facial features with normal intelligence. This study aims to provide insight into the comprehensive evaluation of clinical, laboratory, and radiological findings, expand the mutational spectrum of the disease, and establish a genotype-phenotype correlation in the present cases.
View Article and Find Full Text PDF3M syndrome patient with a novel mutation: A case report.
World J Clin Cases
March 2024
Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Article Synopsis
- - 3M syndrome is a rare genetic disorder characterized by severe growth retardation and specific physical features, but typically does not affect mental development or organs; identified genes are crucial for diagnosis.
- - A case study highlighted a patient with unusual symptoms and no typical facial features associated with 3M syndrome, leading to genetic testing which revealed a new and previously unreported genetic variant.
- - The findings underscore the variability in clinical features of 3M syndrome and the importance of genetic testing for accurate diagnosis, contributing to a broader understanding of the disorder's molecular profile.
Longitudinal skeletal growth and growth plate morphological characteristics of chondro-tissue specific CUL7 knockout mice.
Ann Anat
April 2024
Department of pediatrics, The Second Hospital of Hebei Medical University, No. 215 of Heping West Road, Xinhua District, Shijiazhuang, 050000, China. Electronic address:
Background: 3 M syndrome is first reported in 1975，which characterized by severe pre- and postnatal growth retardation, skeletal malformation and facial dysmorphism. These three genes (CUL7, OBSL1 and CCDC8) have been identified to be respond for 3 M syndrome, of which CUL7 is accounting for approximately 70%. To date, the molecular mechanism underlying the pathogenesis of 3 M syndrome remains poorly understood.
View Article and Find Full Text PDFPrenatal diagnosis and preimplantation genetics testing of 3M syndrome in a Chinese family with novel biallelic variants of CUL7.
Mol Genet Genomic Med
January 2024
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Article Synopsis
- 3M syndrome is a rare genetic disorder that causes growth deficiencies and distinct facial features, typically diagnosed through genetic testing for specific mutations in the CUL7, OBSL1, or CCDC8 genes.
- In a case study, a Chinese couple faced challenges with an abnormal pregnancy showing 3M phenotypes; whole-exome sequencing revealed two new mutations in the CUL7 gene as potential causes.
- After genetic counseling, the couple chose preimplantation genetic testing to reduce the risk of having another child affected by 3M syndrome, leading to the successful birth of a healthy baby.
Genetic testing and diagnostic strategies of fetal skeletal dysplasia: a preliminary study in Wuhan, China.
Orphanet J Rare Dis
October 2023
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China.
Background: Fetal skeletal dysplasia is a diverse group of degenerative diseases of bone and cartilage disorders that can lead to movement disorder and even death. This study aims to evaluate the diagnostic yield of sonographic examination and genetic testing for fetal skeletal dysplasia.
Methods: From September 2015 to April 2021, the study investigated 24 cases with suspected short-limb fetuses, which were obtained from Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.
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