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Small deletions of SATB2 cause some of the clinical features of the 2q33.1 microdeletion syndrome.

Rosenfeld JA, Ballif BC, Lucas A, Spence EJ, Powell C, Aylsworth AS, Torchia BA, Shaffer LG - PLoS ONE (2009)

Bottom Line: Two of the individuals had behavioral problems.Only one of the subjects presented here had a cleft palate, suggesting reduced penetrance for this feature.Our results suggest that deletion of SATB2 is responsible for several of the clinical features associated with 2q32q33 microdeletion syndrome.

View Article: PubMed Central - PubMed

Affiliation: Signature Genomic Laboratories LLC, Spokane, WA, USA.

ABSTRACT
Recurrent deletions of 2q32q33 have recently been reported as a new microdeletion syndrome. Clinical features of this syndrome include severe mental retardation, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties and cleft or high palate. The commonly deleted region contains at least seven genes. Haploinsufficiency of one of these genes, SATB2, a DNA-binding protein that regulates gene expression, has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome. In this study we describe three individuals with smaller microdeletions of this region, within 2q33.1. The deletions ranged in size from 173.1 kb to 185.2 kb and spanned part of SATB2. Review of clinical records showed similar clinical features among these individuals, including severe developmental delay and tooth abnormalities. Two of the individuals had behavioral problems. Only one of the subjects presented here had a cleft palate, suggesting reduced penetrance for this feature. Our results suggest that deletion of SATB2 is responsible for several of the clinical features associated with 2q32q33 microdeletion syndrome.

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Analysis of individuals with microdeletions of 2q33.1.(A–D) Oligonucleotide microarray profiles for (A) normal chromosome 2, (B) a single-copy loss of 183.6 kb at 2q33.1 in subject 1, (C) a single-copy loss 173.1 kb at 2q33.1 in subject 2, and (D) a single-copy loss of 185.2 kb at 2q33.1 in subject 3. For the microarray plots, clones are ordered on the x axis according to physical mapping positions with proximal 2q33.1 to the left and distal 2q33.1 to the right. (E) Summary of the deletion sizes in individuals with microdeletions encompassing 2q33.1. Green bars indicate the approximate deletion sizes in individuals in the Van Buggenhout et al. [11] study (upper portion of diagram) and the current study (bottom of diagram). The SATB2 gene is indicated by a red box.
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pone-0006568-g001: Analysis of individuals with microdeletions of 2q33.1.(A–D) Oligonucleotide microarray profiles for (A) normal chromosome 2, (B) a single-copy loss of 183.6 kb at 2q33.1 in subject 1, (C) a single-copy loss 173.1 kb at 2q33.1 in subject 2, and (D) a single-copy loss of 185.2 kb at 2q33.1 in subject 3. For the microarray plots, clones are ordered on the x axis according to physical mapping positions with proximal 2q33.1 to the left and distal 2q33.1 to the right. (E) Summary of the deletion sizes in individuals with microdeletions encompassing 2q33.1. Green bars indicate the approximate deletion sizes in individuals in the Van Buggenhout et al. [11] study (upper portion of diagram) and the current study (bottom of diagram). The SATB2 gene is indicated by a red box.

Mentions: We identified three individuals with microdeletion of 2q33.1 among our patient population. We characterized the deletions in more detail using a high-density 105K oligonucleotide microarray. Microarray analysis identified single-copy losses of the region containing SATB2 in each of the individuals (Figure 1). A 183.6 kb deletion spanning all but the 5′ end of the SATB2 gene at 2q33.1 (chr2:199,837,205–200,020,800) was found in subject 1; a 173.1 kb deletion at 2q33.1 within the SATB2 gene (chr2:199,860,227–200,033,309) was found in subject 2; and a 185.2 kb deletion at 2q33.1 encompassing all but the 3′ end of SATB2 (chr2:199,860,027–200,045,201) was found in subject 3. The only gene contained in each of the three deletions was SATB2. No other clinically significant gains or losses were detected in these individuals. A search of the Database of Genomic Variants (projects.tcag.ca/variation/) showed seven normal individuals have been reported with small deletions in SATB2; however, each of the deletions was entirely within an intron of the gene.


Small deletions of SATB2 cause some of the clinical features of the 2q33.1 microdeletion syndrome.

Rosenfeld JA, Ballif BC, Lucas A, Spence EJ, Powell C, Aylsworth AS, Torchia BA, Shaffer LG - PLoS ONE (2009)

Analysis of individuals with microdeletions of 2q33.1.(A–D) Oligonucleotide microarray profiles for (A) normal chromosome 2, (B) a single-copy loss of 183.6 kb at 2q33.1 in subject 1, (C) a single-copy loss 173.1 kb at 2q33.1 in subject 2, and (D) a single-copy loss of 185.2 kb at 2q33.1 in subject 3. For the microarray plots, clones are ordered on the x axis according to physical mapping positions with proximal 2q33.1 to the left and distal 2q33.1 to the right. (E) Summary of the deletion sizes in individuals with microdeletions encompassing 2q33.1. Green bars indicate the approximate deletion sizes in individuals in the Van Buggenhout et al. [11] study (upper portion of diagram) and the current study (bottom of diagram). The SATB2 gene is indicated by a red box.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2719055&req=5

pone-0006568-g001: Analysis of individuals with microdeletions of 2q33.1.(A–D) Oligonucleotide microarray profiles for (A) normal chromosome 2, (B) a single-copy loss of 183.6 kb at 2q33.1 in subject 1, (C) a single-copy loss 173.1 kb at 2q33.1 in subject 2, and (D) a single-copy loss of 185.2 kb at 2q33.1 in subject 3. For the microarray plots, clones are ordered on the x axis according to physical mapping positions with proximal 2q33.1 to the left and distal 2q33.1 to the right. (E) Summary of the deletion sizes in individuals with microdeletions encompassing 2q33.1. Green bars indicate the approximate deletion sizes in individuals in the Van Buggenhout et al. [11] study (upper portion of diagram) and the current study (bottom of diagram). The SATB2 gene is indicated by a red box.
Mentions: We identified three individuals with microdeletion of 2q33.1 among our patient population. We characterized the deletions in more detail using a high-density 105K oligonucleotide microarray. Microarray analysis identified single-copy losses of the region containing SATB2 in each of the individuals (Figure 1). A 183.6 kb deletion spanning all but the 5′ end of the SATB2 gene at 2q33.1 (chr2:199,837,205–200,020,800) was found in subject 1; a 173.1 kb deletion at 2q33.1 within the SATB2 gene (chr2:199,860,227–200,033,309) was found in subject 2; and a 185.2 kb deletion at 2q33.1 encompassing all but the 3′ end of SATB2 (chr2:199,860,027–200,045,201) was found in subject 3. The only gene contained in each of the three deletions was SATB2. No other clinically significant gains or losses were detected in these individuals. A search of the Database of Genomic Variants (projects.tcag.ca/variation/) showed seven normal individuals have been reported with small deletions in SATB2; however, each of the deletions was entirely within an intron of the gene.

Bottom Line: Two of the individuals had behavioral problems.Only one of the subjects presented here had a cleft palate, suggesting reduced penetrance for this feature.Our results suggest that deletion of SATB2 is responsible for several of the clinical features associated with 2q32q33 microdeletion syndrome.

View Article: PubMed Central - PubMed

Affiliation: Signature Genomic Laboratories LLC, Spokane, WA, USA.

ABSTRACT
Recurrent deletions of 2q32q33 have recently been reported as a new microdeletion syndrome. Clinical features of this syndrome include severe mental retardation, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties and cleft or high palate. The commonly deleted region contains at least seven genes. Haploinsufficiency of one of these genes, SATB2, a DNA-binding protein that regulates gene expression, has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome. In this study we describe three individuals with smaller microdeletions of this region, within 2q33.1. The deletions ranged in size from 173.1 kb to 185.2 kb and spanned part of SATB2. Review of clinical records showed similar clinical features among these individuals, including severe developmental delay and tooth abnormalities. Two of the individuals had behavioral problems. Only one of the subjects presented here had a cleft palate, suggesting reduced penetrance for this feature. Our results suggest that deletion of SATB2 is responsible for several of the clinical features associated with 2q32q33 microdeletion syndrome.

Show MeSH
Related in: MedlinePlus