Changes in facial appearance from neonate to adult in 3-M syndrome patient with novel CUL7 gene mutations
-
Kosei Hasegawa
,
Hiroyuki Tanaka
Abstract
3-M syndrome (OMIM #273750, #612921, and #614205) is a rare autosomal recessive growth disorder that is characterized by pre- and postnatal growth retardation, normal intelligence, and characteristic faces. This syndrome also has characteristic radiological features, such as slender long bones and tall vertebral bodies. Three genes, cullin 7 (CUL7), coiled-coil domain containing 8, and obscurin-like 1 are genetic candidates of 3-M syndrome. Patients with 3-M syndrome have a characteristic facial appearance, including a triangular face, frontal bossing, an anteverted nose, dolichocephaly, and a long philtrum. However, information on adult 3-M syndrome patients, including facial appearance, is scarce. We report an adult female with 3-M syndrome that was caused by novel compound heterozygous mutations (c.4023-1 G>A in splice acceptor site of exon 22 and c.4359_4363dupGGCTG in exon 23) in the CUL7 gene. We also report the growth chart and changes in facial appearance of this patient from the neonate to adult.
Acknowledgments
We thank our patient for her voluntary participation in this report.
Author contributions: Study design: Kosei Hasegawa and Hiroyuki Tanaka. Clinical data collection: Kosei Hasegawa, Yosuke Higuchi, and Miho Yamashita. Drafting the manuscript: Kosei Hasegawa and Hiroyuki Tanaka. Revising manuscript content: Hiroyuki Tanaka and Hirokazu Tsukahara. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Ethical approval: All procedures performed in this study were in accordance with the ethical standards of Okayama University Hospital and with the 1964 Helsinki declaration and its later amendments.
Informed consent: Informed consent was obtained from this patient.
References
1. Huber C, Munnich A, Cormier-Daire V. The 3M syndrome. Best Pract Res Clin Endocrinol Metab 2011;25:143–51.10.1016/j.beem.2010.08.015Search in Google Scholar PubMed
2. Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, et al. Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A 2011;155A:943–68.10.1002/ajmg.a.33909Search in Google Scholar PubMed PubMed Central
3. Hanson D, Murray PG, O’Sullivan J, Urquhart J, Daly S, et al. Exome sequencing identifies 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;89:148–53.10.1016/j.ajhg.2011.05.028Search in Google Scholar PubMed PubMed Central
4. Hanson D, Murray PG, Sud A, Temtamy SA, Aglan M, et al. The primordial growth disorder 3-M syndrome connects ubiquitination to the cytoskeletal adaptor OBSL1. Am J Hum Genet 2009;84:801–6.10.1016/j.ajhg.2009.04.021Search in Google Scholar PubMed PubMed Central
5. Huber C, Dias-Santagata D, Glaser A, O’Sullivan J, Brauner R, et al. Identification of mutations in CUL7 in 3-M syndrome. Nat Genet 2005;37:1119–24.10.1038/ng1628Search in Google Scholar PubMed
6. Hanson D, Murray PG, Coulson T, Sud A, Omokanye A, et al. Mutations in CUL7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factor signalling. J Mol Endocrinol 2012;49:267–75.10.1530/JME-12-0034Search in Google Scholar PubMed
7. Reese MG, Eeckman FH, Kulp D, Haussler D. Improved splice site detection in Genie. J Comput Biol 1997;4;311–23.10.1089/cmb.1997.4.311Search in Google Scholar PubMed
8. Al-Dosari MS, Al-Shammari M, Shaheen R, Faqeih E, Alghofely MA, et al. 3M syndrome: an easily recognizable yet underdiagnosed cause of proportionate short stature. J Pediatr 2012;161:139–45 e1.10.1016/j.jpeds.2011.12.051Search in Google Scholar PubMed
9. Dauber A, Stoler J, Hechter E, Safer J, Hirschhorn JN. Whole exome sequencing reveals a novel mutation in CUL7 in a patient with an undiagnosed growth disorder. J Pediatr 2013;162:202–4 e1.10.1016/j.jpeds.2012.07.055Search in Google Scholar PubMed PubMed Central
10. Tachibana K, Suwa S. A study on the height of children with achondroplasia based on a nationwide survey. Annu Rep Growth Sci Assoc 1993;17:431–44.Search in Google Scholar
11. Holder-Espinasse M, Irving M, Cormier-Daire V. Clinical utility gene card for: 3-M syndrome – update 2013. Eur J Hum Genet 2014;22. Doi: 10.1038/ejhg.2013.156.10.1038/ejhg.2013.156Search in Google Scholar PubMed PubMed Central
©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- REVIEW
- Obesity-associated sympathetic overactivity in children and adolescents: the role of catecholamine resistance in lipid metabolism
- MINI REVIEW
- Idiopathic infantile hypercalcemia: case report and review of the literature
- ORIGINAL ARTICLES
- Levothyroxine replacement in primary congenital hypothyroidism: the higher the initial dose the higher the rate of overtreatment
- Effect of auditory guided imagery on glucose levels and on glycemic control in children with type 1 diabetes mellitus
- Kidney injury molecule-1 and neutrophil gelatinase associated lipocalin in normoalbuminuric diabetic children
- Use of the triglyceride to HDL cholesterol ratio for assessing insulin sensitivity in overweight and obese children in rural Appalachia
- Carotid intima media thickness in obese children: is there an association with hyperlipidemia?
- Schoolchildren born VLBW or VLGA show height-related changes in body composition and muscle function but no evidence of metabolic syndrome risk factors. Results from the NEOLONG study
- Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty – a case series
- Urinary myo-inositol levels in Japanese schoolchildren with normal glucose tolerance
- Barriers in communication and available resources to facilitate conversation about infertility with girls diagnosed with Turner syndrome
- Analysis of the PAX8 gene in 32 children with thyroid dysgenesis and functional characterization of a promoter variant
- Decrease of small dense LDL and lipoprotein-associated phospholipase A2 due to human growth hormone treatment in short children with growth hormone deficiency and small for gestational age status
- Rare and curable renin-mediated hypertension: a series of six cases and a literature review
- CASE REPORTS
- Vulvar fetal rhabdomyoma mimicking 46XX sex differentiation disorder
- Simultaneous occurrence of diabetic ketoacidosis, thyroid storm, and multiple cerebral infarctions due to Moyamoya disease
- Brown-Vialetto-Van Laere syndrome: two siblings with a new mutation and dramatic therapeutic effect of high-dose riboflavin
- Lipomatous nevus and urethral caruncle mistaken for ambiguous genitalia in a female infant
- Thyrotropin-secreting pituitary adenoma in an 11-year-old boy with type 1 autoimmune polyglandular syndrome
- Changes in facial appearance from neonate to adult in 3-M syndrome patient with novel CUL7 gene mutations
Articles in the same Issue
- Frontmatter
- REVIEW
- Obesity-associated sympathetic overactivity in children and adolescents: the role of catecholamine resistance in lipid metabolism
- MINI REVIEW
- Idiopathic infantile hypercalcemia: case report and review of the literature
- ORIGINAL ARTICLES
- Levothyroxine replacement in primary congenital hypothyroidism: the higher the initial dose the higher the rate of overtreatment
- Effect of auditory guided imagery on glucose levels and on glycemic control in children with type 1 diabetes mellitus
- Kidney injury molecule-1 and neutrophil gelatinase associated lipocalin in normoalbuminuric diabetic children
- Use of the triglyceride to HDL cholesterol ratio for assessing insulin sensitivity in overweight and obese children in rural Appalachia
- Carotid intima media thickness in obese children: is there an association with hyperlipidemia?
- Schoolchildren born VLBW or VLGA show height-related changes in body composition and muscle function but no evidence of metabolic syndrome risk factors. Results from the NEOLONG study
- Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty – a case series
- Urinary myo-inositol levels in Japanese schoolchildren with normal glucose tolerance
- Barriers in communication and available resources to facilitate conversation about infertility with girls diagnosed with Turner syndrome
- Analysis of the PAX8 gene in 32 children with thyroid dysgenesis and functional characterization of a promoter variant
- Decrease of small dense LDL and lipoprotein-associated phospholipase A2 due to human growth hormone treatment in short children with growth hormone deficiency and small for gestational age status
- Rare and curable renin-mediated hypertension: a series of six cases and a literature review
- CASE REPORTS
- Vulvar fetal rhabdomyoma mimicking 46XX sex differentiation disorder
- Simultaneous occurrence of diabetic ketoacidosis, thyroid storm, and multiple cerebral infarctions due to Moyamoya disease
- Brown-Vialetto-Van Laere syndrome: two siblings with a new mutation and dramatic therapeutic effect of high-dose riboflavin
- Lipomatous nevus and urethral caruncle mistaken for ambiguous genitalia in a female infant
- Thyrotropin-secreting pituitary adenoma in an 11-year-old boy with type 1 autoimmune polyglandular syndrome
- Changes in facial appearance from neonate to adult in 3-M syndrome patient with novel CUL7 gene mutations
