3-M syndrome – a primordial short stature disorder with novel CUL7 mutation in two Indian patients
-
Radha Rama Devi Akella
Abstract
Objective
To evaluate the cause of short stature in children.
Case presentation
Two children with suspected skeletal dysplasia and short stature were evaluated.
Conclusions
The 3-M syndrome is a primordial growth disorder manifesting severe postnatal growth restriction, skeletal anomalies and prominent fleshy heels. The 3-M syndrome is a genetically heterogeneous disorder and the phenotype is similar. This is a rare autosomal recessive disorder with normal intellect. Two affected children have been identified by whole-exome sequencing. One patient harboured a compound heterozygous variant and the other was a homozygous missense variant. The genetic diagnosis helped in counselling the families and facilitated prenatal diagnosis in one (case 1) family.
-
Research funding: None.
-
Author contributions: This study is done only by a single author.
-
Competing interests: There is no financial, personal or professional conflict in connection with the evaluated manuscript.
-
Informed consent: Informed consent, including written permission from the patient’s mother, was obtained.
-
Ethical approval: All investigations conducted have followed the tenets of the Helsinki Declaration. The review board of Rainbow children hospital approved the study.
References
1. Miller, JD, McKusick, VA, Malvaux, P, Temtamy, S, Salinas, C. The 3-M syndrome: a heritable low birthweight dwarfism. Birth Defects 1975;11:39–47.Search in Google Scholar
2. Hanson, D, Murray, PG, O’Sullivan, J, Urquhart, J, Daly, S, Bhaskar, SS, et al.. CCDC8 mutations in 3-M syndrome, suggesting that CCDC8 contributes in a pathway with CUL7 and OBSL1 to control human growth. Am J Hum Genet 2011;89:148–53. https://doi.org/10.1016/j.ajhg.2011.05.028.Search in Google Scholar PubMed PubMed Central
3. Huber, C, Munnich, A, Cormier-Daire, V. The 3M syndrome. Best Pract Res Clin Endocrinol Metabol 2011;25:143–51. https://doi.org/10.1016/j.beem.2010.08.015.Search in Google Scholar PubMed
4. Patton, MA. Russell-Silver syndrome. J Med Genet 1988;25:557–60. https://doi.org/10.1136/jmg.25.8.557.Search in Google Scholar PubMed PubMed Central
5. Shaikh, S, Suresh, K, Shettigari, G, Kantharia, S, Kurva, J, Cherian, S, et al.. Novel mutation in Cul7 gene in a family diagnosed with 3M syndrome. J Genet 2019;98:21. https://doi.org/10.1007/s12041-019-1057-6.Search in Google Scholar
6. Kumar, MH, Kumar, MS, Siva Kumar, V, Sabitha Hari, Kumar. An adult with 3-M syndrome. BMJ Case Rep 2015;1–3. https://doi.org/10.1136/bcr-2015-211429.Search in Google Scholar PubMed PubMed Central
7. Hanson, D, Murray, PG, Coulson, T, Sud, A, Omokanye, A, Stratta, E, et al.. Mutations in CULT7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factorsignalling. J Mol Endocrinol 2012;49:267–75. https://doi.org/10.1530/jme-12-0034.Search in Google Scholar
8. Maksimova, N, Hara, K, Miyashia, A, Nikolaeva, I, Shiga, A, Nogovicina, A, et al.. Clinical, molecular and histopathological features of SS syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia. Med Genet 2007;44(12):772–8. https://doi.org/10.1136/jmg.2007.051979.Search in Google Scholar PubMed PubMed Central
9. Keskin, M, Şahin, NM, Kurnaz, E, Bayramoğlu, E, Erdeve, ŞS, et al.. A rare cause of short stature: 3M syndrome in a patient with novel mutation in OBSL1 gene. J Clin Res Pediatr Endocrinol 2017;9(1):91–4. https://doi.org/10.4274/jcrpe.3238.Search in Google Scholar PubMed PubMed Central
10. Van der Wala, G, Otten, BJ, Brunner, HG, van der Burgt, I. 3-M syndrome: description of six new patients with review of the literature. Clin Dysmorphol 2001;10(4):241–52. https://doi.org/10.1097/00019605-200110000-00002.Search in Google Scholar PubMed
11. Demir, K, Altıncık, A, Böber, E. Severe short stature due to 3-M syndrome with a novel OBSL1 gene mutation. Pediatr Endocrinol Metab 2013;26(1-2):147–50. https://doi.org/10.1515/jpem-2012-0239.Search in Google Scholar PubMed
12. Güven, A, Nurcan Cebeci, A. 3M syndrome: a report of four cases in two families. Clin Res Pediatr Endocrinol 2011;3(3):154–9. https://doi.org/10.4274/jcrpe.v3i3.30.Search in Google Scholar PubMed PubMed Central
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review Article
- Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management
- Original Articles
- Weight changes of children in 1 year during COVID-19 pandemic
- Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease
- Rates of adrenal insufficiency using a monoclonal vs. polyclonal cortisol assay
- Hyperinsulinemic hypoglycemia in growth restricted convalescent preterm neonates: clinical characteristics and impediments to early diagnosis
- Identification of three novel pathogenic mutations in cystathionine beta-synthase gene of Pakistani intellectually disabled patients
- The prevalence of incidental finding of gynecomastia on thoracic computed tomography in the pediatric age group
- The prevalence of hypertension and elevated blood pressure and its correlation with overweight/obesity among students aged 6–17 years in Suzhou
- Investigation of androgen receptor gene CAG repeat length polymorphism in pubertal gynecomastia
- A single-centre study of genetic mutations, audiology, echocardiogram and pulmonary function in Saudi children with osteogenesis imperfecta
- A 10-year retrospective single-center study of alpha-fetoprotein and beta-human chorionic gonadotropin in Romanian children with (para)gonadal tumors and cysts
- Clinical, pathological and molecular spectrum of patients with glycogen storage diseases in Pakistan
- Allelic dropout in PAH affecting the results of genetic diagnosis in phenylketonuria
- Short Communication
- Role of the SARS-CoV-2 virus in the appearance of new onset type 1 diabetes mellitus in children in Gran Canaria, Spain
- Case Reports
- 3-M syndrome – a primordial short stature disorder with novel CUL7 mutation in two Indian patients
- The coincidence of two rare diseases with opposite metabolic phenotype: a child with congenital hyperinsulinism and Bloom syndrome
- Growth hormone deficiency in a child with benign hereditary chorea caused by a de novo mutation of the TITF1/NKX2-1 gene
- Identification of a novel mutation in the PHKA2 gene in a child with liver cirrhosis
Articles in the same Issue
- Frontmatter
- Review Article
- Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management
- Original Articles
- Weight changes of children in 1 year during COVID-19 pandemic
- Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease
- Rates of adrenal insufficiency using a monoclonal vs. polyclonal cortisol assay
- Hyperinsulinemic hypoglycemia in growth restricted convalescent preterm neonates: clinical characteristics and impediments to early diagnosis
- Identification of three novel pathogenic mutations in cystathionine beta-synthase gene of Pakistani intellectually disabled patients
- The prevalence of incidental finding of gynecomastia on thoracic computed tomography in the pediatric age group
- The prevalence of hypertension and elevated blood pressure and its correlation with overweight/obesity among students aged 6–17 years in Suzhou
- Investigation of androgen receptor gene CAG repeat length polymorphism in pubertal gynecomastia
- A single-centre study of genetic mutations, audiology, echocardiogram and pulmonary function in Saudi children with osteogenesis imperfecta
- A 10-year retrospective single-center study of alpha-fetoprotein and beta-human chorionic gonadotropin in Romanian children with (para)gonadal tumors and cysts
- Clinical, pathological and molecular spectrum of patients with glycogen storage diseases in Pakistan
- Allelic dropout in PAH affecting the results of genetic diagnosis in phenylketonuria
- Short Communication
- Role of the SARS-CoV-2 virus in the appearance of new onset type 1 diabetes mellitus in children in Gran Canaria, Spain
- Case Reports
- 3-M syndrome – a primordial short stature disorder with novel CUL7 mutation in two Indian patients
- The coincidence of two rare diseases with opposite metabolic phenotype: a child with congenital hyperinsulinism and Bloom syndrome
- Growth hormone deficiency in a child with benign hereditary chorea caused by a de novo mutation of the TITF1/NKX2-1 gene
- Identification of a novel mutation in the PHKA2 gene in a child with liver cirrhosis
