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Isolated Sagittal Synostosis in a Boy with Craniofrontonasal Dysplasia and a Novel EFNB1 Mutation.

Chauhan BK, Hoover JM, Scanga H, Medsinge A, Arnold GL, Nischal KK - Plast Reconstr Surg Glob Open (2015)

Bottom Line: A 7-year-old boy presented with hypertelorism, broad nasal root, midfacial hypoplasia, mandibular prognathia, ptosis, and scaphocephaly was clinically diagnosed with CFNS.Three-dimensional computed tomographic scans confirmed the isolated sagittal synostosis.To the best of our knowledge, this is the only reported incident of CFNS in a male child exhibiting isolated sagittal synostosis.

View Article: PubMed Central - PubMed

Affiliation: UPMC Eye Center, Children's Hospital of Pittsburgh, Pittsburgh, Pa.; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pa.; and Division of Medical Genetics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pa.

ABSTRACT
Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder that shows greater severity in females and is largely attributed to mutations in EFNB1. A 7-year-old boy presented with hypertelorism, broad nasal root, midfacial hypoplasia, mandibular prognathia, ptosis, and scaphocephaly was clinically diagnosed with CFNS. Three-dimensional computed tomographic scans confirmed the isolated sagittal synostosis. His mother also showed clinical features of CFNS, but less severe. Genetic tests uncovered a novel C to T mutation at nucleotide 466 (c.466C>T) in exon 1 of EFNB1 for both. To the best of our knowledge, this is the only reported incident of CFNS in a male child exhibiting isolated sagittal synostosis.

No MeSH data available.


Related in: MedlinePlus

A, Chromatogram showing the C to T missense mutation at nucleotide 466 (c.466C>T) in EFNB1. The top portion is the reference genome and the bottom portion is the patient sample showing the missense mutation at position 466 (denoted by ^). B, Missense mutation, p.Arg156Cys (denoted by ^), in the RBD of EFNB1. The protein structure of human EFNB1 is shown at the top. Amino acid sequence alignments from several vertebrate species in the region of the missense mutation are at the bottom, together with the human sequence alignments for human EFNB1, 2, and 3 in the same region. The numbers refer to amino acid positions for the human EFNB1 protein. Chk indicates chicken; Gor, gorilla; Hu, human; M, mouse; RBD, receptor-binding domain; TM, transmembrane; XL, Xenopus laevis (frog); Zf, zebrafish.
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Figure 3: A, Chromatogram showing the C to T missense mutation at nucleotide 466 (c.466C>T) in EFNB1. The top portion is the reference genome and the bottom portion is the patient sample showing the missense mutation at position 466 (denoted by ^). B, Missense mutation, p.Arg156Cys (denoted by ^), in the RBD of EFNB1. The protein structure of human EFNB1 is shown at the top. Amino acid sequence alignments from several vertebrate species in the region of the missense mutation are at the bottom, together with the human sequence alignments for human EFNB1, 2, and 3 in the same region. The numbers refer to amino acid positions for the human EFNB1 protein. Chk indicates chicken; Gor, gorilla; Hu, human; M, mouse; RBD, receptor-binding domain; TM, transmembrane; XL, Xenopus laevis (frog); Zf, zebrafish.

Mentions: All genetic testing were conducted in laboratories certified under the Clinical Laboratory Improvement Amendments of 1988. Previous genetic testing of the patient included a karyotype at a 600 G-band level of resolution and an oligoarray, both of which demonstrated a normal chromosomal complement. After the ophthalmic examination, venous blood was drawn and genomic DNA extracted. Sequencing of exons 1 through 5 of EFNB1 revealed a novel C to T mutation at nucleotide 466 in exon 1 (c.466C>T) (Fig. 3A), which changes a codon for the nonpolar arginine to the polar cysteine at amino acid 156 (p.Arg156Cys) (Fig. 3B). This arginine is highly conserved from mammals, chicken, frogs, and zebrafish in addition to being conserved in EFNB2 and EFNB3. The amino acid change is at the terminus end of the EFNB1 ephrin receptor-binding domain, the main functional domain. The mother was found to have the same mutation with a less severe phenotype, whereas the younger brother was negative for site-specific mutation analysis and had no signs of CFNS. Written informed consent was obtained from the mother of the child for being included in the study.


Isolated Sagittal Synostosis in a Boy with Craniofrontonasal Dysplasia and a Novel EFNB1 Mutation.

Chauhan BK, Hoover JM, Scanga H, Medsinge A, Arnold GL, Nischal KK - Plast Reconstr Surg Glob Open (2015)

A, Chromatogram showing the C to T missense mutation at nucleotide 466 (c.466C>T) in EFNB1. The top portion is the reference genome and the bottom portion is the patient sample showing the missense mutation at position 466 (denoted by ^). B, Missense mutation, p.Arg156Cys (denoted by ^), in the RBD of EFNB1. The protein structure of human EFNB1 is shown at the top. Amino acid sequence alignments from several vertebrate species in the region of the missense mutation are at the bottom, together with the human sequence alignments for human EFNB1, 2, and 3 in the same region. The numbers refer to amino acid positions for the human EFNB1 protein. Chk indicates chicken; Gor, gorilla; Hu, human; M, mouse; RBD, receptor-binding domain; TM, transmembrane; XL, Xenopus laevis (frog); Zf, zebrafish.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4494497&req=5

Figure 3: A, Chromatogram showing the C to T missense mutation at nucleotide 466 (c.466C>T) in EFNB1. The top portion is the reference genome and the bottom portion is the patient sample showing the missense mutation at position 466 (denoted by ^). B, Missense mutation, p.Arg156Cys (denoted by ^), in the RBD of EFNB1. The protein structure of human EFNB1 is shown at the top. Amino acid sequence alignments from several vertebrate species in the region of the missense mutation are at the bottom, together with the human sequence alignments for human EFNB1, 2, and 3 in the same region. The numbers refer to amino acid positions for the human EFNB1 protein. Chk indicates chicken; Gor, gorilla; Hu, human; M, mouse; RBD, receptor-binding domain; TM, transmembrane; XL, Xenopus laevis (frog); Zf, zebrafish.
Mentions: All genetic testing were conducted in laboratories certified under the Clinical Laboratory Improvement Amendments of 1988. Previous genetic testing of the patient included a karyotype at a 600 G-band level of resolution and an oligoarray, both of which demonstrated a normal chromosomal complement. After the ophthalmic examination, venous blood was drawn and genomic DNA extracted. Sequencing of exons 1 through 5 of EFNB1 revealed a novel C to T mutation at nucleotide 466 in exon 1 (c.466C>T) (Fig. 3A), which changes a codon for the nonpolar arginine to the polar cysteine at amino acid 156 (p.Arg156Cys) (Fig. 3B). This arginine is highly conserved from mammals, chicken, frogs, and zebrafish in addition to being conserved in EFNB2 and EFNB3. The amino acid change is at the terminus end of the EFNB1 ephrin receptor-binding domain, the main functional domain. The mother was found to have the same mutation with a less severe phenotype, whereas the younger brother was negative for site-specific mutation analysis and had no signs of CFNS. Written informed consent was obtained from the mother of the child for being included in the study.

Bottom Line: A 7-year-old boy presented with hypertelorism, broad nasal root, midfacial hypoplasia, mandibular prognathia, ptosis, and scaphocephaly was clinically diagnosed with CFNS.Three-dimensional computed tomographic scans confirmed the isolated sagittal synostosis.To the best of our knowledge, this is the only reported incident of CFNS in a male child exhibiting isolated sagittal synostosis.

View Article: PubMed Central - PubMed

Affiliation: UPMC Eye Center, Children's Hospital of Pittsburgh, Pittsburgh, Pa.; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pa.; and Division of Medical Genetics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pa.

ABSTRACT
Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder that shows greater severity in females and is largely attributed to mutations in EFNB1. A 7-year-old boy presented with hypertelorism, broad nasal root, midfacial hypoplasia, mandibular prognathia, ptosis, and scaphocephaly was clinically diagnosed with CFNS. Three-dimensional computed tomographic scans confirmed the isolated sagittal synostosis. His mother also showed clinical features of CFNS, but less severe. Genetic tests uncovered a novel C to T mutation at nucleotide 466 (c.466C>T) in exon 1 of EFNB1 for both. To the best of our knowledge, this is the only reported incident of CFNS in a male child exhibiting isolated sagittal synostosis.

No MeSH data available.


Related in: MedlinePlus