Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome.

Lina Basel-Vanagaite; Bruno Dallapiccola; Ramiro Ramirez-Solis; Alexandra Segref; Holger Thiele; Andrew Edwards; Mark J Arends; Xavier Miró; Jacqueline K White; Julie Désir; Marc Abramowicz; Maria Lisa Dentici; Francesca Lepri; Kay Hofmann; Adi Har-Zahav; Edward Ryder; Natasha A Karp; Jeanne Estabel; Anna-Karin B Gerdin; Christine Podrini; Neil J Ingham; Janine Altmüller; Gudrun Nürnberg; Peter Frommolt; Sonia Abdelhak; Metsada Pasmanik-Chor; Osnat Konen; Richard I Kelley; Mordechai Shohat; Peter Nürnberg; Jonathan Flint; Karen P Steel; Thorsten Hoppe; Christian Kubisch; David J Adams; Guntram Borck

Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome.

Standard

Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome. / Basel-Vanagaite, Lina; Dallapiccola, Bruno; Ramirez-Solis, Ramiro; Segref, Alexandra; Thiele, Holger; Edwards, Andrew; Arends, Mark J; Miró, Xavier; White, Jacqueline K; Désir, Julie; Abramowicz, Marc; Dentici, Maria Lisa; Lepri, Francesca; Hofmann, Kay; Har-Zahav, Adi; Ryder, Edward; Karp, Natasha A; Estabel, Jeanne; Gerdin, Anna-Karin B; Podrini, Christine; Ingham, Neil J; Altmüller, Janine; Nürnberg, Gudrun; Frommolt, Peter; Abdelhak, Sonia; Pasmanik-Chor, Metsada; Konen, Osnat; Kelley, Richard I; Shohat, Mordechai; Nürnberg, Peter; Flint, Jonathan; Steel, Karen P; Hoppe, Thorsten; Kubisch, Christian; Adams, David J; Borck, Guntram.

In: AM J HUM GENET, Vol. 91, No. 6, 6, 2012, p. 998-1010.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Basel-Vanagaite, L, Dallapiccola, B, Ramirez-Solis, R, Segref, A, Thiele, H, Edwards, A, Arends, MJ, Miró, X, White, JK, Désir, J, Abramowicz, M, Dentici, ML, Lepri, F, Hofmann, K, Har-Zahav, A, Ryder, E, Karp, NA, Estabel, J, Gerdin, A-KB, Podrini, C, Ingham, NJ, Altmüller, J, Nürnberg, G, Frommolt, P, Abdelhak, S, Pasmanik-Chor, M, Konen, O, Kelley, RI, Shohat, M, Nürnberg, P, Flint, J, Steel, KP, Hoppe, T, Kubisch, C, Adams, DJ & Borck, G 2012, 'Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome.', AM J HUM GENET, vol. 91, no. 6, 6, pp. 998-1010. <http://www.ncbi.nlm.nih.gov/pubmed/23200864?dopt=Citation>

APA

Basel-Vanagaite, L., Dallapiccola, B., Ramirez-Solis, R., Segref, A., Thiele, H., Edwards, A., Arends, M. J., Miró, X., White, J. K., Désir, J., Abramowicz, M., Dentici, M. L., Lepri, F., Hofmann, K., Har-Zahav, A., Ryder, E., Karp, N. A., Estabel, J., Gerdin, A-K. B., ... Borck, G. (2012). Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome. AM J HUM GENET, 91(6), 998-1010. [6]. http://www.ncbi.nlm.nih.gov/pubmed/23200864?dopt=Citation

Vancouver

Basel-Vanagaite L, Dallapiccola B, Ramirez-Solis R, Segref A, Thiele H, Edwards A et al. Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome. AM J HUM GENET. 2012;91(6):998-1010. 6.

Bibtex

@article{95e9ddd01ec44c5d8a46a78d6d4985a2,

title = "Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome.",

abstract = "Ubiquitination plays a crucial role in neurodevelopment as exemplified by Angelman syndrome, which is caused by genetic alterations of the ubiquitin ligase-encoding UBE3A gene. Although the function of UBE3A has been widely studied, little is known about its paralog UBE3B. By using exome and capillary sequencing, we here identify biallelic UBE3B mutations in four patients from three unrelated families presenting an autosomal-recessive blepharophimosis-ptosis-intellectual-disability syndrome characterized by developmental delay, growth retardation with a small head circumference, facial dysmorphisms, and low cholesterol levels. UBE3B encodes an uncharacterized E3 ubiquitin ligase. The identified UBE3B variants include one frameshift and two splice-site mutations as well as a missense substitution affecting the highly conserved HECT domain. Disruption of mouse Ube3b leads to reduced viability and recapitulates key aspects of the human disorder, such as reduced weight and brain size and a downregulation of cholesterol synthesis. We establish that the probable Caenorhabditis elegans ortholog of UBE3B, oxi-1, functions in the ubiquitin/proteasome system in vivo and is especially required under oxidative stress conditions. Our data reveal the pleiotropic effects of UBE3B deficiency and reinforce the physiological importance of ubiquitination in neuronal development and function in mammals.",

keywords = "Animals, Humans, Male, Female, Child, Child, Preschool, Genotype, Infant, Mice, Mice, Knockout, Magnetic Resonance Imaging, Mutation, Amino Acid Sequence, Base Sequence, Syndrome, Alleles, Oxidative Stress, Brain/pathology, Exome, Blepharophimosis/diagnosis/*genetics, Blepharoptosis/diagnosis/*genetics, Caenorhabditis elegans/genetics/metabolism, Central Nervous System, Facies, Intellectual Disability/diagnosis/*genetics, Ubiquitin-Protein Ligases/deficiency/*genetics, Animals, Humans, Male, Female, Child, Child, Preschool, Genotype, Infant, Mice, Mice, Knockout, Magnetic Resonance Imaging, Mutation, Amino Acid Sequence, Base Sequence, Syndrome, Alleles, Oxidative Stress, Brain/pathology, Exome, Blepharophimosis/diagnosis/*genetics, Blepharoptosis/diagnosis/*genetics, Caenorhabditis elegans/genetics/metabolism, Central Nervous System, Facies, Intellectual Disability/diagnosis/*genetics, Ubiquitin-Protein Ligases/deficiency/*genetics",

author = "Lina Basel-Vanagaite and Bruno Dallapiccola and Ramiro Ramirez-Solis and Alexandra Segref and Holger Thiele and Andrew Edwards and Arends, {Mark J} and Xavier Mir{\'o} and White, {Jacqueline K} and Julie D{\'e}sir and Marc Abramowicz and Dentici, {Maria Lisa} and Francesca Lepri and Kay Hofmann and Adi Har-Zahav and Edward Ryder and Karp, {Natasha A} and Jeanne Estabel and Gerdin, {Anna-Karin B} and Christine Podrini and Ingham, {Neil J} and Janine Altm{\"u}ller and Gudrun N{\"u}rnberg and Peter Frommolt and Sonia Abdelhak and Metsada Pasmanik-Chor and Osnat Konen and Kelley, {Richard I} and Mordechai Shohat and Peter N{\"u}rnberg and Jonathan Flint and Steel, {Karen P} and Thorsten Hoppe and Christian Kubisch and Adams, {David J} and Guntram Borck",

year = "2012",

language = "English",

volume = "91",

pages = "998--1010",

journal = "AM J HUM GENET",

issn = "0002-9297",

publisher = "Cell Press",

number = "6",

}

RIS

TY - JOUR

T1 - Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome.

AU - Basel-Vanagaite, Lina

AU - Dallapiccola, Bruno

AU - Ramirez-Solis, Ramiro

AU - Segref, Alexandra

AU - Thiele, Holger

AU - Edwards, Andrew

AU - Arends, Mark J

AU - Miró, Xavier

AU - White, Jacqueline K

AU - Désir, Julie

AU - Abramowicz, Marc

AU - Dentici, Maria Lisa

AU - Lepri, Francesca

AU - Hofmann, Kay

AU - Har-Zahav, Adi

AU - Ryder, Edward

AU - Karp, Natasha A

AU - Estabel, Jeanne

AU - Gerdin, Anna-Karin B

AU - Podrini, Christine

AU - Ingham, Neil J

AU - Altmüller, Janine

AU - Nürnberg, Gudrun

AU - Frommolt, Peter

AU - Abdelhak, Sonia

AU - Pasmanik-Chor, Metsada

AU - Konen, Osnat

AU - Kelley, Richard I

AU - Shohat, Mordechai

AU - Nürnberg, Peter

AU - Flint, Jonathan

AU - Steel, Karen P

AU - Hoppe, Thorsten

AU - Kubisch, Christian

AU - Adams, David J

AU - Borck, Guntram

PY - 2012

Y1 - 2012

N2 - Ubiquitination plays a crucial role in neurodevelopment as exemplified by Angelman syndrome, which is caused by genetic alterations of the ubiquitin ligase-encoding UBE3A gene. Although the function of UBE3A has been widely studied, little is known about its paralog UBE3B. By using exome and capillary sequencing, we here identify biallelic UBE3B mutations in four patients from three unrelated families presenting an autosomal-recessive blepharophimosis-ptosis-intellectual-disability syndrome characterized by developmental delay, growth retardation with a small head circumference, facial dysmorphisms, and low cholesterol levels. UBE3B encodes an uncharacterized E3 ubiquitin ligase. The identified UBE3B variants include one frameshift and two splice-site mutations as well as a missense substitution affecting the highly conserved HECT domain. Disruption of mouse Ube3b leads to reduced viability and recapitulates key aspects of the human disorder, such as reduced weight and brain size and a downregulation of cholesterol synthesis. We establish that the probable Caenorhabditis elegans ortholog of UBE3B, oxi-1, functions in the ubiquitin/proteasome system in vivo and is especially required under oxidative stress conditions. Our data reveal the pleiotropic effects of UBE3B deficiency and reinforce the physiological importance of ubiquitination in neuronal development and function in mammals.

AB - Ubiquitination plays a crucial role in neurodevelopment as exemplified by Angelman syndrome, which is caused by genetic alterations of the ubiquitin ligase-encoding UBE3A gene. Although the function of UBE3A has been widely studied, little is known about its paralog UBE3B. By using exome and capillary sequencing, we here identify biallelic UBE3B mutations in four patients from three unrelated families presenting an autosomal-recessive blepharophimosis-ptosis-intellectual-disability syndrome characterized by developmental delay, growth retardation with a small head circumference, facial dysmorphisms, and low cholesterol levels. UBE3B encodes an uncharacterized E3 ubiquitin ligase. The identified UBE3B variants include one frameshift and two splice-site mutations as well as a missense substitution affecting the highly conserved HECT domain. Disruption of mouse Ube3b leads to reduced viability and recapitulates key aspects of the human disorder, such as reduced weight and brain size and a downregulation of cholesterol synthesis. We establish that the probable Caenorhabditis elegans ortholog of UBE3B, oxi-1, functions in the ubiquitin/proteasome system in vivo and is especially required under oxidative stress conditions. Our data reveal the pleiotropic effects of UBE3B deficiency and reinforce the physiological importance of ubiquitination in neuronal development and function in mammals.

KW - Animals

KW - Humans

KW - Male

KW - Female

KW - Child

KW - Child, Preschool

KW - Genotype

KW - Infant

KW - Mice

KW - Mice, Knockout

KW - Magnetic Resonance Imaging

KW - Mutation

KW - Amino Acid Sequence

KW - Base Sequence

KW - Syndrome

KW - Alleles

KW - Oxidative Stress

KW - Brain/pathology

KW - Exome

KW - Blepharophimosis/diagnosis/genetics

KW - Blepharoptosis/diagnosis/genetics

KW - Caenorhabditis elegans/genetics/metabolism

KW - Central Nervous System

KW - Facies

KW - Intellectual Disability/diagnosis/genetics

KW - Ubiquitin-Protein Ligases/deficiency/genetics