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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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(A) Facial image of subject 1 at age 2 years, 9 months. (B) Facial image of subject 1 at age 9 years, 8 months. Subject is in mixed dentition and is missing her maxillary central incisors. (C) Front and (D) profile facial images of subject 2 at age 10 years. Note the broad nasal midsection, small mandible, and macrocephaly.
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pone-0006568-g002: (A) Facial image of subject 1 at age 2 years, 9 months. (B) Facial image of subject 1 at age 9 years, 8 months. Subject is in mixed dentition and is missing her maxillary central incisors. (C) Front and (D) profile facial images of subject 2 at age 10 years. Note the broad nasal midsection, small mandible, and macrocephaly.

Mentions: Clinical information was available for subjects 1–3 (Table 1). Subject 1 is a 9-year 8-month old female with severe mental retardation, dysmorphic features, and behavior problems. Family history was negative for any individuals with similar developmental delays. The subject was born to a 30-year-old mother via a somewhat difficult vaginal delivery following a pregnancy complicated by gestational diabetes. Fetal activity was normal. Exposures were denied. There was perinatal distress with difficulty in delivering the head. Labor was induced. Birth weight was 8 pounds 9 ounces. She had a fractured clavicle and some transient tachypnea and was discharged home at 7 days. Developmental delays were noted in early childhood, and intelligence testing placed her IQ below 50. She had delayed primary dentition, with eruption of her first tooth at age 2. At age 9 years 8 months she has 20 words, four to five signs, and one two-word phrase. Head MRI at age 2 was normal, and head CT at age 7 was also unremarkable. She has a heart murmur with no known further workup. Dysmorphic features include frontal bossing, a long and narrow face with a prominent maxillary arch, a class II malocclusion with relative micrognathia, slightly large ears, a smooth upper lip, and a smooth philtrum (Figure 2A–B). The subject was uncooperative with direct examination of her palate, but her history is not consistent with any palatal clefting. At age 9 years 8 months height is at the 25th–50th percentile, weight is at the 50th–75th percentile, and head circumference is at the 75th percentile. She has normal dentition. The subject is very social, repeats actions multiple times, frequently washes her hands, likes to have her hair washed, has touch avoidance, has good eye contact, is somewhat photophobic, and has nodules on the dorsal surfaces of her fifth fingers bilaterally consistent with the effects of chewing on her hands.


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)

(A) Facial image of subject 1 at age 2 years, 9 months. (B) Facial image of subject 1 at age 9 years, 8 months. Subject is in mixed dentition and is missing her maxillary central incisors. (C) Front and (D) profile facial images of subject 2 at age 10 years. Note the broad nasal midsection, small mandible, and macrocephaly.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2719055&req=5

pone-0006568-g002: (A) Facial image of subject 1 at age 2 years, 9 months. (B) Facial image of subject 1 at age 9 years, 8 months. Subject is in mixed dentition and is missing her maxillary central incisors. (C) Front and (D) profile facial images of subject 2 at age 10 years. Note the broad nasal midsection, small mandible, and macrocephaly.
Mentions: Clinical information was available for subjects 1–3 (Table 1). Subject 1 is a 9-year 8-month old female with severe mental retardation, dysmorphic features, and behavior problems. Family history was negative for any individuals with similar developmental delays. The subject was born to a 30-year-old mother via a somewhat difficult vaginal delivery following a pregnancy complicated by gestational diabetes. Fetal activity was normal. Exposures were denied. There was perinatal distress with difficulty in delivering the head. Labor was induced. Birth weight was 8 pounds 9 ounces. She had a fractured clavicle and some transient tachypnea and was discharged home at 7 days. Developmental delays were noted in early childhood, and intelligence testing placed her IQ below 50. She had delayed primary dentition, with eruption of her first tooth at age 2. At age 9 years 8 months she has 20 words, four to five signs, and one two-word phrase. Head MRI at age 2 was normal, and head CT at age 7 was also unremarkable. She has a heart murmur with no known further workup. Dysmorphic features include frontal bossing, a long and narrow face with a prominent maxillary arch, a class II malocclusion with relative micrognathia, slightly large ears, a smooth upper lip, and a smooth philtrum (Figure 2A–B). The subject was uncooperative with direct examination of her palate, but her history is not consistent with any palatal clefting. At age 9 years 8 months height is at the 25th–50th percentile, weight is at the 50th–75th percentile, and head circumference is at the 75th percentile. She has normal dentition. The subject is very social, repeats actions multiple times, frequently washes her hands, likes to have her hair washed, has touch avoidance, has good eye contact, is somewhat photophobic, and has nodules on the dorsal surfaces of her fifth fingers bilaterally consistent with the effects of chewing on her hands.

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