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De novo three-way chromosome translocation 46,XY,t(4;6;21)(p16;p21.1;q21) in a male with cleidocranial dysplasia.

Purandare SM, Mendoza-Londono R, Yatsenko SA, Napierala D, Scott DA, Sibai T, Casas K, Wilson P, Lee J, Muneer R, Leonard JC, Ramji FG, Lachman R, Li S, Stankiewicz P, Lee B, Mulvihill JJ - Am. J. Med. Genet. A (2008)

Bottom Line: Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia associated with cranial, clavicular, and dental anomalies.We hypothesize that the proband's CCD has arisen from disruption of the developmentally regulated gene RUNX2 at the 6p21 breakpoint, due to a position effect mutation which may have altered the expression of the gene.Further studies might unravel a new regulatory element for RUNX2.

View Article: PubMed Central - PubMed

Affiliation: Section of Genetics, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.

ABSTRACT
Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia associated with cranial, clavicular, and dental anomalies. It is caused by mutations in the RUNX2 gene, which encodes an osteoblast-specific transcription factor and maps to chromosome 6p21. We report clinical and molecular cytogenetic studies in a patient with clinical features of CCD including wormian bones, delayed fontanel closure, hypoplastic clavicles and pubic rami, and supernumerary dentition. Additional abnormalities of bone growth and connective tissue, including easy bruisability, scarring, bleeding, joint hypermobility, and developmental delay were also observed. Molecular cytogenetic studies identified a de novo apparently balanced three-way translocation 46,XY,t(4;6;21)(p16;p21.1;q21). Further mapping revealed the breakpoint on 6p21 to be approximately 50 kb upstream of exon 1 of the RUNX2 gene, with RUNX2 being intact on the derivative chromosome 6. We hypothesize that the proband's CCD has arisen from disruption of the developmentally regulated gene RUNX2 at the 6p21 breakpoint, due to a position effect mutation which may have altered the expression of the gene. Further studies might unravel a new regulatory element for RUNX2.

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Related in: MedlinePlus

Clinical findings at age 14 years. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
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fig01: Clinical findings at age 14 years. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Mentions: Abnormalities of bone growth and connective tissue evolved over time. At 14 years of age (Fig. 1), he complained of easy bruisability, scarring, bleeding, joint pain, increased shoulder motion, and occasional shortness of breath during heavy exercise. Pubertal development was delayed. Height, weight, and head circumference were at the 25th, 50th, and 80th centiles, respectively. He had soft skin with multiple bruises. His face was asymmetric with leftward deviation of the nose. There was kyphosis with a slight rightward deviation. He had pes planus along with hypoplastic fourth and fifth toenails, bilaterally. He could actively dislocate his thumb, knees, and hip. He had bilateral contractures at the elbows, and two cafe-au-lait macules. Endocrine studies showed normal gonadotropin levels. At age 16 years, height was at the 20th centile, weight was at the 80th centile, and occipital–frontal circumference was at the 98th centile. Pubertal development was Tanner III for male pubic hair. Bilaterally there was decreased supination and extension of the elbows and shoulders. The clavicles are diminutive allowing excessive adduction of the shoulders.


De novo three-way chromosome translocation 46,XY,t(4;6;21)(p16;p21.1;q21) in a male with cleidocranial dysplasia.

Purandare SM, Mendoza-Londono R, Yatsenko SA, Napierala D, Scott DA, Sibai T, Casas K, Wilson P, Lee J, Muneer R, Leonard JC, Ramji FG, Lachman R, Li S, Stankiewicz P, Lee B, Mulvihill JJ - Am. J. Med. Genet. A (2008)

Clinical findings at age 14 years. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2663417&req=5

fig01: Clinical findings at age 14 years. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Mentions: Abnormalities of bone growth and connective tissue evolved over time. At 14 years of age (Fig. 1), he complained of easy bruisability, scarring, bleeding, joint pain, increased shoulder motion, and occasional shortness of breath during heavy exercise. Pubertal development was delayed. Height, weight, and head circumference were at the 25th, 50th, and 80th centiles, respectively. He had soft skin with multiple bruises. His face was asymmetric with leftward deviation of the nose. There was kyphosis with a slight rightward deviation. He had pes planus along with hypoplastic fourth and fifth toenails, bilaterally. He could actively dislocate his thumb, knees, and hip. He had bilateral contractures at the elbows, and two cafe-au-lait macules. Endocrine studies showed normal gonadotropin levels. At age 16 years, height was at the 20th centile, weight was at the 80th centile, and occipital–frontal circumference was at the 98th centile. Pubertal development was Tanner III for male pubic hair. Bilaterally there was decreased supination and extension of the elbows and shoulders. The clavicles are diminutive allowing excessive adduction of the shoulders.

Bottom Line: Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia associated with cranial, clavicular, and dental anomalies.We hypothesize that the proband's CCD has arisen from disruption of the developmentally regulated gene RUNX2 at the 6p21 breakpoint, due to a position effect mutation which may have altered the expression of the gene.Further studies might unravel a new regulatory element for RUNX2.

View Article: PubMed Central - PubMed

Affiliation: Section of Genetics, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.

ABSTRACT
Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia associated with cranial, clavicular, and dental anomalies. It is caused by mutations in the RUNX2 gene, which encodes an osteoblast-specific transcription factor and maps to chromosome 6p21. We report clinical and molecular cytogenetic studies in a patient with clinical features of CCD including wormian bones, delayed fontanel closure, hypoplastic clavicles and pubic rami, and supernumerary dentition. Additional abnormalities of bone growth and connective tissue, including easy bruisability, scarring, bleeding, joint hypermobility, and developmental delay were also observed. Molecular cytogenetic studies identified a de novo apparently balanced three-way translocation 46,XY,t(4;6;21)(p16;p21.1;q21). Further mapping revealed the breakpoint on 6p21 to be approximately 50 kb upstream of exon 1 of the RUNX2 gene, with RUNX2 being intact on the derivative chromosome 6. We hypothesize that the proband's CCD has arisen from disruption of the developmentally regulated gene RUNX2 at the 6p21 breakpoint, due to a position effect mutation which may have altered the expression of the gene. Further studies might unravel a new regulatory element for RUNX2.

Show MeSH
Related in: MedlinePlus