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Nonsense mutations in FZD2 cause autosomal-dominant omodysplasia: Robinow syndrome-like phenotypes.
Am J Med Genet A. 2018 Mar; 176(3):739-742.AJ

Abstract

Omodysplasia-2 (OMOD2; OMIM%16475) is a rare autosomal dominant (AD) skeletal dysplasia characterized by shortened humeri, short first metacarpal, craniofacial dysmorphism (frontal bossing, depressed nasal bridge, bifid nasal tip, and long philtrum), and variable degrees of genitourinary anomalies. This clinical phenotype overlaps with that of AD type Robinow syndrome. Recently, a mutation in FZD2 encoding a Frizzled Class Receptor 2 has been identified in a family with AD omodysplasia (an affected girl and her affected mother). Here, we present the second report on a heterozygous novel nonsense FZD2 mutation in OMOD2 or Robinow syndrome-like phenotype. The proband was a 16-year-old boy, who has been followed from infancy to adolescence. He presented with rhizomelic short stature with elbow restriction, mild facial dysmorphism (depressed broad bridge, short nose, anteverted nostrils, long philtrum, and low-set ears), and genital hypoplasia. Radiological examination in infancy showed short, broad humeri with relatively narrow distal ends, mildly broad femora, thick proximal ulnae with hypoplastic, dislocated proximal radii, and short first metacarpals. The abnormal skeletal pattern was persistent in adolescence; however, the humeri and femora became less undermodeled, while the humeri and radii became mildly bowed. Molecular analysis identified a de novo, heterozygous, nonsense mutation (c.1640C>A, p.S547*) in FZD2. The affected codon was next to the previously reported mutation (p.Trp548*). The results indicate that OMOD2 or Robinow syndome-like phenotype can be caused by a heterozygous nonsense FZD2 mutation impairing Wnt signaling. Further molecular studies will permit better clarification of the phenotypic spectrum in patients with OMOD2.

Authors+Show Affiliations

Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.Intractable Disease Center, Saitama Medical University Hospital, Saitama, Japan.Department of Pediatrics, Saitama Medical University, Saitama, Japan.Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29383834

Citation

Nagasaki, Keisuke, et al. "Nonsense Mutations in FZD2 Cause Autosomal-dominant Omodysplasia: Robinow Syndrome-like Phenotypes." American Journal of Medical Genetics. Part A, vol. 176, no. 3, 2018, pp. 739-742.
Nagasaki K, Nishimura G, Kikuchi T, et al. Nonsense mutations in FZD2 cause autosomal-dominant omodysplasia: Robinow syndrome-like phenotypes. Am J Med Genet A. 2018;176(3):739-742.
Nagasaki, K., Nishimura, G., Kikuchi, T., Nyuzuki, H., Sasaki, S., Ogawa, Y., & Saitoh, A. (2018). Nonsense mutations in FZD2 cause autosomal-dominant omodysplasia: Robinow syndrome-like phenotypes. American Journal of Medical Genetics. Part A, 176(3), 739-742. https://doi.org/10.1002/ajmg.a.38623
Nagasaki K, et al. Nonsense Mutations in FZD2 Cause Autosomal-dominant Omodysplasia: Robinow Syndrome-like Phenotypes. Am J Med Genet A. 2018;176(3):739-742. PubMed PMID: 29383834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nonsense mutations in FZD2 cause autosomal-dominant omodysplasia: Robinow syndrome-like phenotypes. AU - Nagasaki,Keisuke, AU - Nishimura,Gen, AU - Kikuchi,Toru, AU - Nyuzuki,Hiromi, AU - Sasaki,Sunao, AU - Ogawa,Yohei, AU - Saitoh,Akihiko, Y1 - 2018/01/31/ PY - 2017/07/10/received PY - 2017/12/05/revised PY - 2018/01/07/accepted PY - 2018/2/1/pubmed PY - 2019/3/1/medline PY - 2018/2/1/entrez KW - FZD2 KW - OMOD2 KW - Wnt signaling KW - short stature KW - shortened humeri SP - 739 EP - 742 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 176 IS - 3 N2 - Omodysplasia-2 (OMOD2; OMIM%16475) is a rare autosomal dominant (AD) skeletal dysplasia characterized by shortened humeri, short first metacarpal, craniofacial dysmorphism (frontal bossing, depressed nasal bridge, bifid nasal tip, and long philtrum), and variable degrees of genitourinary anomalies. This clinical phenotype overlaps with that of AD type Robinow syndrome. Recently, a mutation in FZD2 encoding a Frizzled Class Receptor 2 has been identified in a family with AD omodysplasia (an affected girl and her affected mother). Here, we present the second report on a heterozygous novel nonsense FZD2 mutation in OMOD2 or Robinow syndrome-like phenotype. The proband was a 16-year-old boy, who has been followed from infancy to adolescence. He presented with rhizomelic short stature with elbow restriction, mild facial dysmorphism (depressed broad bridge, short nose, anteverted nostrils, long philtrum, and low-set ears), and genital hypoplasia. Radiological examination in infancy showed short, broad humeri with relatively narrow distal ends, mildly broad femora, thick proximal ulnae with hypoplastic, dislocated proximal radii, and short first metacarpals. The abnormal skeletal pattern was persistent in adolescence; however, the humeri and femora became less undermodeled, while the humeri and radii became mildly bowed. Molecular analysis identified a de novo, heterozygous, nonsense mutation (c.1640C>A, p.S547*) in FZD2. The affected codon was next to the previously reported mutation (p.Trp548*). The results indicate that OMOD2 or Robinow syndome-like phenotype can be caused by a heterozygous nonsense FZD2 mutation impairing Wnt signaling. Further molecular studies will permit better clarification of the phenotypic spectrum in patients with OMOD2. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/29383834/Nonsense_mutations_in_FZD2_cause_autosomal_dominant_omodysplasia:_Robinow_syndrome_like_phenotypes_ L2 - https://doi.org/10.1002/ajmg.a.38623 DB - PRIME DP - Unbound Medicine ER -