DVL3 Alleles Resulting in a-1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome (2024)

White, J. J., Mazzeu, J. F., Hoischen, A., Bayram, Y., Withers, M., Gezdirici, A., Kimonis, V., Steehouwer, M., Jhangiani, S. N., Muzny, D. M., Gibbs, R. A., Van Bon, B. W. M., Sutton, V. R., Lupski, J. R., Brunner, H. G., & Carvalho, C. M. B. (2016). DVL3 Alleles Resulting in a-1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome. American Journal of Human Genetics, 98(3), 553-561. https://doi.org/10.1016/j.ajhg.2016.01.005

White, Janson J. ; Mazzeu, Juliana F. ; Hoischen, Alexander et al. / DVL3 Alleles Resulting in a-1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome. In: American Journal of Human Genetics. 2016 ; Vol. 98, No. 3. pp. 553-561.

@article{4181a7f523994f5da7388f5db4b85e69,

title = "DVL3 Alleles Resulting in a-1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome",

abstract = "Robinow syndrome is a rare congenital disorder characterized by mesomelic limb shortening, genital hypoplasia, and distinctive facial features. Recent reports have identified, in individuals with dominant Robinow syndrome, a specific type of variant characterized by being uniformly located in the penultimate exon of DVL1 and resulting in a-1 frameshift allele with a premature termination codon that escapes nonsense-mediated decay. Here, we studied a cohort of individuals who had been clinically diagnosed with Robinow syndrome but who had not received a molecular diagnosis from variant studies of DVL1, WNT5A, and ROR2. Because of the uniform location of frameshift variants in DVL1-mediated Robinow syndrome and the functional redundancy of DVL1, DVL2, and DVL3, we elected to pursue direct Sanger sequencing of the penultimate exon of DVL1 and its paralogs DVL2 and DVL3 to search for potential disease-associated variants. Remarkably, targeted sequencing identified five unrelated individuals harboring heterozygous, de novo frameshift variants in DVL3, including two splice acceptor mutations and three 1 bp deletions. Similar to the variants observed in DVL1-mediated Robinow syndrome, all variants in DVL3 result in a-1 frameshift, indicating that these highly specific alterations might be a common cause of dominant Robinow syndrome. Here, we review the current knowledge of these peculiar variant alleles in DVL1-A nd DVL3-mediated Robinow syndrome and further elucidate the phenotypic features present in subjects with DVL1 and DVL3 frameshift mutations.",

author = "White, {Janson J.} and Mazzeu, {Juliana F.} and Alexander Hoischen and Yavuz Bayram and Marjorie Withers and Alper Gezdirici and Virginia Kimonis and Marloes Steehouwer and Jhangiani, {Shalini N.} and Muzny, {Donna M.} and Gibbs, {Richard A.} and {Van Bon}, {Bregje W.M.} and Sutton, {V. Reid} and Lupski, {James R.} and Brunner, {Han G.} and Carvalho, {Claudia M.B.}",

note = "Publisher Copyright: {\textcopyright} 2016 The American Society of Human Genetics.",

year = "2016",

month = mar,

day = "3",

doi = "10.1016/j.ajhg.2016.01.005",

language = "English",

volume = "98",

pages = "553--561",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "3",

}

White, JJ, Mazzeu, JF, Hoischen, A, Bayram, Y, Withers, M, Gezdirici, A, Kimonis, V, Steehouwer, M, Jhangiani, SN, Muzny, DM, Gibbs, RA, Van Bon, BWM, Sutton, VR, Lupski, JR, Brunner, HG & Carvalho, CMB 2016, 'DVL3 Alleles Resulting in a-1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome', American Journal of Human Genetics, vol. 98, no. 3, pp. 553-561. https://doi.org/10.1016/j.ajhg.2016.01.005

DVL3 Alleles Resulting in a-1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome. / White, Janson J.; Mazzeu, Juliana F.; Hoischen, Alexander et al.
In: American Journal of Human Genetics, Vol. 98, No. 3, 03.03.2016, p. 553-561.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - DVL3 Alleles Resulting in a-1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome

AU - White, Janson J.

AU - Mazzeu, Juliana F.

AU - Hoischen, Alexander

AU - Bayram, Yavuz

AU - Withers, Marjorie

AU - Gezdirici, Alper

AU - Kimonis, Virginia

AU - Steehouwer, Marloes

AU - Jhangiani, Shalini N.

AU - Muzny, Donna M.

AU - Gibbs, Richard A.

AU - Van Bon, Bregje W.M.

AU - Sutton, V. Reid

AU - Lupski, James R.

AU - Brunner, Han G.

AU - Carvalho, Claudia M.B.

N1 - Publisher Copyright:© 2016 The American Society of Human Genetics.

PY - 2016/3/3

Y1 - 2016/3/3

N2 - Robinow syndrome is a rare congenital disorder characterized by mesomelic limb shortening, genital hypoplasia, and distinctive facial features. Recent reports have identified, in individuals with dominant Robinow syndrome, a specific type of variant characterized by being uniformly located in the penultimate exon of DVL1 and resulting in a-1 frameshift allele with a premature termination codon that escapes nonsense-mediated decay. Here, we studied a cohort of individuals who had been clinically diagnosed with Robinow syndrome but who had not received a molecular diagnosis from variant studies of DVL1, WNT5A, and ROR2. Because of the uniform location of frameshift variants in DVL1-mediated Robinow syndrome and the functional redundancy of DVL1, DVL2, and DVL3, we elected to pursue direct Sanger sequencing of the penultimate exon of DVL1 and its paralogs DVL2 and DVL3 to search for potential disease-associated variants. Remarkably, targeted sequencing identified five unrelated individuals harboring heterozygous, de novo frameshift variants in DVL3, including two splice acceptor mutations and three 1 bp deletions. Similar to the variants observed in DVL1-mediated Robinow syndrome, all variants in DVL3 result in a-1 frameshift, indicating that these highly specific alterations might be a common cause of dominant Robinow syndrome. Here, we review the current knowledge of these peculiar variant alleles in DVL1-A nd DVL3-mediated Robinow syndrome and further elucidate the phenotypic features present in subjects with DVL1 and DVL3 frameshift mutations.

AB - Robinow syndrome is a rare congenital disorder characterized by mesomelic limb shortening, genital hypoplasia, and distinctive facial features. Recent reports have identified, in individuals with dominant Robinow syndrome, a specific type of variant characterized by being uniformly located in the penultimate exon of DVL1 and resulting in a-1 frameshift allele with a premature termination codon that escapes nonsense-mediated decay. Here, we studied a cohort of individuals who had been clinically diagnosed with Robinow syndrome but who had not received a molecular diagnosis from variant studies of DVL1, WNT5A, and ROR2. Because of the uniform location of frameshift variants in DVL1-mediated Robinow syndrome and the functional redundancy of DVL1, DVL2, and DVL3, we elected to pursue direct Sanger sequencing of the penultimate exon of DVL1 and its paralogs DVL2 and DVL3 to search for potential disease-associated variants. Remarkably, targeted sequencing identified five unrelated individuals harboring heterozygous, de novo frameshift variants in DVL3, including two splice acceptor mutations and three 1 bp deletions. Similar to the variants observed in DVL1-mediated Robinow syndrome, all variants in DVL3 result in a-1 frameshift, indicating that these highly specific alterations might be a common cause of dominant Robinow syndrome. Here, we review the current knowledge of these peculiar variant alleles in DVL1-A nd DVL3-mediated Robinow syndrome and further elucidate the phenotypic features present in subjects with DVL1 and DVL3 frameshift mutations.

UR - http://www.scopus.com/inward/record.url?scp=84960075536&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2016.01.005

DO - 10.1016/j.ajhg.2016.01.005

M3 - Article

C2 - 26924530

AN - SCOPUS:84960075536

SN - 0002-9297

VL - 98

SP - 553

EP - 561

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 3

ER -

White JJ, Mazzeu JF, Hoischen A, Bayram Y, Withers M, Gezdirici A et al. DVL3 Alleles Resulting in a-1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome. American Journal of Human Genetics. 2016 Mar 3;98(3):553-561. doi: 10.1016/j.ajhg.2016.01.005