Further expanding the mutational spectrum and investigation of genotype-phenotype correlation in 3M syndrome.

Abstract

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.

• Authors: Pelin Ozlem Simsek-Kiper, Ekim Taskiran, Can Kosukcu, Umut Ece Arslan, Valérie Cormier-Daire, Nazlı Gonc, Alev Ozon, Ayfer Alikasifoglu, Nurgun Kandemir, Gulen Eda Utine, Yasemin Alanay, Mehmet Alikasifoglu, Koray Boduroglu
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 179 Issue 7 Pg. 1157-1172 (07 2019) ISSN: 1552-4833 [Electronic] United States
• PMID: 30980518 (Publication Type: Journal Article)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• BMP2 protein, human
• Bone Morphogenetic Protein 2
• CUL7 protein, human
• Cullin Proteins
• Cytoskeletal Proteins
• OBSL1 protein, human

Topics

• Adolescent
• Base Sequence
• Bone Morphogenetic Protein 2 (deficiency, genetics)
• Child
• Child, Preschool
• Chromosomes, Human, Pair 20
• Cohort Studies
• Cullin Proteins (genetics, metabolism)
• Cytoskeletal Proteins (genetics, metabolism)
• Dwarfism (diagnosis, genetics, metabolism, pathology)
• Female
• Fetus
• Gene Expression
• Genetic Association Studies
• Genotype
• Humans
• Infant
• Infant, Newborn
• Male
• Muscle Hypotonia (diagnosis, genetics, metabolism, pathology)
• Mutation
• Phenotype
• Spine (abnormalities, metabolism, pathology)
• Exome Sequencing