TY - JOUR

T1 - Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B

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

N1 - © 2011 John Wiley & Sons A/S.

PY - 2011

Y1 - 2011

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 Phenotype-genotype comparison of the translocation patient to seven unpublished patients with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual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

VL - 82

SP - 248

EP - 255

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 3

ER -