Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B

Christina Halgren Hansen; S Kjaergaard; M Bak; Claus Hansen; Zahra Elschich; Claire Marie Anderson; Karen Friis Henriksen; Helle Hjalgrim; M Kirchhoff; Ek Bijlsma; M Nielsen; Ns den Hollander; Cal Ruivenkamp; B Isidor; C Le Caignec; R Zannolli; M Mucciolo; A Renieri; F Mari; B-M Anderlid; J Andrieux; A Dieux; N Tommerup; I Bache

doi:10.1111/j.1399-0004.2011.01755.x

Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B

Christina Halgren Hansen, S Kjaergaard, M Bak, Claus Hansen, Zahra Elschich, Claire Marie Anderson, Karen Friis Henriksen, Helle Hjalgrim, M Kirchhoff, Ek Bijlsma, M Nielsen, Ns den Hollander, Cal Ruivenkamp, B Isidor, C Le Caignec, R Zannolli, M Mucciolo, A Renieri, F Mari, B-M AnderlidJ Andrieux, A Dieux, N Tommerup, I Bache

87 Citations (Scopus)

Abstract

Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Corpus callosum abnormalities are common brain malformations with a wide clinical spectrum ranging from severe intellectual disability to normal cognitive function. The etiology is expected to be genetic in as much as 30-50% of the cases, but the underlying genetic cause remains unknown in the majority of cases. By next-generation mate-pair sequencing we mapped the chromosomal breakpoints of a patient with a de novo balanced translocation, t(1;6)(p31;q25), agenesis of corpus callosum (CC), intellectual disability, severe speech impairment, and autism. The chromosome 6 breakpoint truncated ARID1B which was also truncated in a recently published translocation patient with a similar phenotype. Quantitative polymerase chain reaction (Q-PCR) data showed that a primer set proximal to the translocation showed increased expression of ARID1B, whereas primer sets spanning or distal to the translocation showed decreased expression in the patient relative to a non-related control set. Phenotype-genotype comparison of the translocation patient to seven unpublished patients with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual disability, severe speech impairment, and autism. Our findings emphasize that ARID1B is important in human brain development and function in general, and in the development of CC and in speech development in particular.

Original language	English
Journal	Clinical Genetics
Volume	82
Issue number	3
Pages (from-to)	248-55
Number of pages	8
ISSN	0009-9163
DOIs	https://doi.org/10.1111/j.1399-0004.2011.01755.x
Publication status	Published - Sept 2012

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Hansen, C. H., Kjaergaard, S., Bak, M., Hansen, C., Elschich, Z., Anderson, C. M., Henriksen, K. F., Hjalgrim, H., Kirchhoff, M., Bijlsma, E., Nielsen, M., den Hollander, N., Ruivenkamp, C., Isidor, B., Le Caignec, C., Zannolli, R., Mucciolo, M., Renieri, A., Mari, F., ... Bache, I. (2012). Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Clinical Genetics, 82(3), 248-55. https://doi.org/10.1111/j.1399-0004.2011.01755.x

Hansen, CH, Kjaergaard, S, Bak, M, Hansen, C, Elschich, Z, Anderson, CM, Henriksen, KF, Hjalgrim, H, Kirchhoff, M, Bijlsma, E, Nielsen, M, den Hollander, N, Ruivenkamp, C, Isidor, B, Le Caignec, C, Zannolli, R, Mucciolo, M, Renieri, A, Mari, F, Anderlid, B-M, Andrieux, J, Dieux, A, Tommerup, N & Bache, I 2012, 'Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B', Clinical Genetics, vol. 82, no. 3, pp. 248-55. https://doi.org/10.1111/j.1399-0004.2011.01755.x

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title = "Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B",

abstract = "Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Corpus callosum abnormalities are common brain malformations with a wide clinical spectrum ranging from severe intellectual disability to normal cognitive function. The etiology is expected to be genetic in as much as 30-50% of the cases, but the underlying genetic cause remains unknown in the majority of cases. By next-generation mate-pair sequencing we mapped the chromosomal breakpoints of a patient with a de novo balanced translocation, t(1;6)(p31;q25), agenesis of corpus callosum (CC), intellectual disability, severe speech impairment, and autism. The chromosome 6 breakpoint truncated ARID1B which was also truncated in a recently published translocation patient with a similar phenotype. Quantitative polymerase chain reaction (Q-PCR) data showed that a primer set proximal to the translocation showed increased expression of ARID1B, whereas primer sets spanning or distal to the translocation showed decreased expression in the patient relative to a non-related control set. Phenotype-genotype comparison of the translocation patient to seven unpublished patients with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual disability, severe speech impairment, and autism. Our findings emphasize that ARID1B is important in human brain development and function in general, and in the development of CC and in speech development in particular.",

author = "Hansen, {Christina Halgren} and S Kjaergaard and M Bak and Claus Hansen and Zahra Elschich and Anderson, {Claire Marie} and Henriksen, {Karen Friis} and Helle Hjalgrim and M Kirchhoff and Ek Bijlsma and M Nielsen and {den Hollander}, Ns and Cal Ruivenkamp and B Isidor and {Le Caignec}, C and R Zannolli and M Mucciolo and A Renieri and F Mari and B-M Anderlid and J Andrieux and A Dieux and N Tommerup and I Bache",

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doi = "10.1111/j.1399-0004.2011.01755.x",

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AU - Hansen, Christina Halgren

AU - Kjaergaard, S

AU - Bak, M

AU - Hansen, Claus

AU - Elschich, Zahra

AU - Anderson, Claire Marie

AU - Henriksen, Karen Friis

AU - Hjalgrim, Helle

AU - Kirchhoff, M

AU - Bijlsma, Ek

AU - Nielsen, M

AU - den Hollander, Ns

AU - Ruivenkamp, Cal

AU - Isidor, B

AU - Le Caignec, C

AU - Zannolli, R

AU - Mucciolo, M

AU - Renieri, A

AU - Mari, F

AU - Anderlid, B-M

AU - Andrieux, J

AU - Dieux, A

AU - Tommerup, N

AU - Bache, I

PY - 2012/9

Y1 - 2012/9

N2 - Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Corpus callosum abnormalities are common brain malformations with a wide clinical spectrum ranging from severe intellectual disability to normal cognitive function. The etiology is expected to be genetic in as much as 30-50% of the cases, but the underlying genetic cause remains unknown in the majority of cases. By next-generation mate-pair sequencing we mapped the chromosomal breakpoints of a patient with a de novo balanced translocation, t(1;6)(p31;q25), agenesis of corpus callosum (CC), intellectual disability, severe speech impairment, and autism. The chromosome 6 breakpoint truncated ARID1B which was also truncated in a recently published translocation patient with a similar phenotype. Quantitative polymerase chain reaction (Q-PCR) data showed that a primer set proximal to the translocation showed increased expression of ARID1B, whereas primer sets spanning or distal to the translocation showed decreased expression in the patient relative to a non-related control set. Phenotype-genotype comparison of the translocation patient to seven unpublished patients with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual disability, severe speech impairment, and autism. Our findings emphasize that ARID1B is important in human brain development and function in general, and in the development of CC and in speech development in particular.

AB - Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Corpus callosum abnormalities are common brain malformations with a wide clinical spectrum ranging from severe intellectual disability to normal cognitive function. The etiology is expected to be genetic in as much as 30-50% of the cases, but the underlying genetic cause remains unknown in the majority of cases. By next-generation mate-pair sequencing we mapped the chromosomal breakpoints of a patient with a de novo balanced translocation, t(1;6)(p31;q25), agenesis of corpus callosum (CC), intellectual disability, severe speech impairment, and autism. The chromosome 6 breakpoint truncated ARID1B which was also truncated in a recently published translocation patient with a similar phenotype. Quantitative polymerase chain reaction (Q-PCR) data showed that a primer set proximal to the translocation showed increased expression of ARID1B, whereas primer sets spanning or distal to the translocation showed decreased expression in the patient relative to a non-related control set. Phenotype-genotype comparison of the translocation patient to seven unpublished patients with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual disability, severe speech impairment, and autism. Our findings emphasize that ARID1B is important in human brain development and function in general, and in the development of CC and in speech development in particular.

U2 - 10.1111/j.1399-0004.2011.01755.x

DO - 10.1111/j.1399-0004.2011.01755.x

M3 - Journal article

C2 - 21801163

SN - 0009-9163

VL - 82

SP - 248

EP - 255

JO - Clinical Genetics

JF - Clinical Genetics

IS - 3

ER -

Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B

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