Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog

Benjamin D. Solomon; Kelly A. Bear; Adrian Wyllie; Amelia A. Keaton; Christele Dubourg; Veronique David; Sandra Mercier; Sylvie Odent; Ute Hehr; Aimee Paulussen; Nancy J. Clegg; Mauricio R. Delgado; Sherri J. Bale; Felicitas Lacbawan; Holly H. Ardinger; Arthur S. Aylsworth; Ntombenhle Louisa Bhengu; Stephen Braddock; Karen Brookhyser; Barbara Burton; Harald Gaspar; Art Grix; Dafne Horovitz; Erin Kanetzke; Hulya Kayserili; Dorit Lev; Sarah M. Nikkel; Mary Norton; Richard Roberts; Howard Saal; G. B. Schaefer; Adele Schneider; Erika K. Smith; Ellen Sowry; M. Anne Spence; Stavit A. Shalev; Carlos E. Steiner; Elizabeth M. Thompson; Thomas L. Winder; Joan Z. Balog; Donald W. Hadley; Nan Zhou; Daniel E. Pineda-Alvarez; Erich Roessler; Maximilian Muenke

doi:10.1136/jmedgenet-2012-101008

Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog

Benjamin D. Solomon, Kelly A. Bear, Adrian Wyllie, Amelia A. Keaton, Christele Dubourg, Veronique David, Sandra Mercier, Sylvie Odent, Ute Hehr, Aimee Paulussen, Nancy J. Clegg, Mauricio R. Delgado, Sherri J. Bale, Felicitas Lacbawan, Holly H. Ardinger, Arthur S. Aylsworth, Ntombenhle Louisa Bhengu, Stephen Braddock, Karen Brookhyser, Barbara BurtonHarald Gaspar, Art Grix, Dafne Horovitz, Erin Kanetzke, Hulya Kayserili, Dorit Lev, Sarah M. Nikkel, Mary Norton, Richard Roberts, Howard Saal, G. B. Schaefer, Adele Schneider, Erika K. Smith, Ellen Sowry, M. Anne Spence, Stavit A. Shalev, Carlos E. Steiner, Elizabeth M. Thompson, Thomas L. Winder, Joan Z. Balog, Donald W. Hadley, Nan Zhou, Daniel E. Pineda-Alvarez, Erich Roessler, Maximilian Muenke^*

^*Corresponding author for this work

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

Abstract

Background Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of nonchromosomal HPE. The severity spectrum is wide, ranging from incompatibility with extrauterine life to isolated midline facial differences. Objective To characterise genetic and clinical findings in individuals with SHH mutations. Methods Through the National Institutes of Health and collaborating centres, DNA from approximately 2000 individuals with HPE spectrum disorders were analysed for SHH variations. Clinical details were examined and combined with published cases. Results This study describes 396 individuals, representing 157 unrelated kindreds, with SHH mutations; 141 (36%) have not been previously reported. SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (p

Original language	English
Pages (from-to)	473-479
Journal	Journal of Medical Genetics
Volume	49
Issue number	7
DOIs	https://doi.org/10.1136/jmedgenet-2012-101008
Publication status	Published - Jul 2012

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Solomon, B. D., Bear, K. A., Wyllie, A., Keaton, A. A., Dubourg, C., David, V., Mercier, S., Odent, S., Hehr, U., Paulussen, A., Clegg, N. J., Delgado, M. R., Bale, S. J., Lacbawan, F., Ardinger, H. H., Aylsworth, A. S., Bhengu, N. L., Braddock, S., Brookhyser, K., ... Muenke, M. (2012). Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog. Journal of Medical Genetics, 49(7), 473-479. https://doi.org/10.1136/jmedgenet-2012-101008

@article{78cc7f04d20a4d7da668c8820e515652,

title = "Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog",

abstract = "Background Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of nonchromosomal HPE. The severity spectrum is wide, ranging from incompatibility with extrauterine life to isolated midline facial differences. Objective To characterise genetic and clinical findings in individuals with SHH mutations. Methods Through the National Institutes of Health and collaborating centres, DNA from approximately 2000 individuals with HPE spectrum disorders were analysed for SHH variations. Clinical details were examined and combined with published cases. Results This study describes 396 individuals, representing 157 unrelated kindreds, with SHH mutations; 141 (36%) have not been previously reported. SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (p",

author = "Solomon, {Benjamin D.} and Bear, {Kelly A.} and Adrian Wyllie and Keaton, {Amelia A.} and Christele Dubourg and Veronique David and Sandra Mercier and Sylvie Odent and Ute Hehr and Aimee Paulussen and Clegg, {Nancy J.} and Delgado, {Mauricio R.} and Bale, {Sherri J.} and Felicitas Lacbawan and Ardinger, {Holly H.} and Aylsworth, {Arthur S.} and Bhengu, {Ntombenhle Louisa} and Stephen Braddock and Karen Brookhyser and Barbara Burton and Harald Gaspar and Art Grix and Dafne Horovitz and Erin Kanetzke and Hulya Kayserili and Dorit Lev and Nikkel, {Sarah M.} and Mary Norton and Richard Roberts and Howard Saal and Schaefer, {G. B.} and Adele Schneider and Smith, {Erika K.} and Ellen Sowry and Spence, {M. Anne} and Shalev, {Stavit A.} and Steiner, {Carlos E.} and Thompson, {Elizabeth M.} and Winder, {Thomas L.} and Balog, {Joan Z.} and Hadley, {Donald W.} and Nan Zhou and Pineda-Alvarez, {Daniel E.} and Erich Roessler and Maximilian Muenke",

year = "2012",

month = jul,

doi = "10.1136/jmedgenet-2012-101008",

language = "English",

volume = "49",

pages = "473--479",

journal = "Journal of Medical Genetics",

issn = "0022-2593",

publisher = "BMJ Publishing Group",

number = "7",

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Solomon, BD, Bear, KA, Wyllie, A, Keaton, AA, Dubourg, C, David, V, Mercier, S, Odent, S, Hehr, U, Paulussen, A, Clegg, NJ, Delgado, MR, Bale, SJ, Lacbawan, F, Ardinger, HH, Aylsworth, AS, Bhengu, NL, Braddock, S, Brookhyser, K, Burton, B, Gaspar, H, Grix, A, Horovitz, D, Kanetzke, E, Kayserili, H, Lev, D, Nikkel, SM, Norton, M, Roberts, R, Saal, H, Schaefer, GB, Schneider, A, Smith, EK, Sowry, E, Spence, MA, Shalev, SA, Steiner, CE, Thompson, EM, Winder, TL, Balog, JZ, Hadley, DW, Zhou, N, Pineda-Alvarez, DE, Roessler, E & Muenke, M 2012, 'Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog', Journal of Medical Genetics, vol. 49, no. 7, pp. 473-479. https://doi.org/10.1136/jmedgenet-2012-101008

TY - JOUR

T1 - Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog

AU - Solomon, Benjamin D.

AU - Bear, Kelly A.

AU - Wyllie, Adrian

AU - Keaton, Amelia A.

AU - Dubourg, Christele

AU - David, Veronique

AU - Mercier, Sandra

AU - Odent, Sylvie

AU - Hehr, Ute

AU - Paulussen, Aimee

AU - Clegg, Nancy J.

AU - Delgado, Mauricio R.

AU - Bale, Sherri J.

AU - Lacbawan, Felicitas

AU - Ardinger, Holly H.

AU - Aylsworth, Arthur S.

AU - Bhengu, Ntombenhle Louisa

AU - Braddock, Stephen

AU - Brookhyser, Karen

AU - Burton, Barbara

AU - Gaspar, Harald

AU - Grix, Art

AU - Horovitz, Dafne

AU - Kanetzke, Erin

AU - Kayserili, Hulya

AU - Lev, Dorit

AU - Nikkel, Sarah M.

AU - Norton, Mary

AU - Roberts, Richard

AU - Saal, Howard

AU - Schaefer, G. B.

AU - Schneider, Adele

AU - Smith, Erika K.

AU - Sowry, Ellen

AU - Spence, M. Anne

AU - Shalev, Stavit A.

AU - Steiner, Carlos E.

AU - Thompson, Elizabeth M.

AU - Winder, Thomas L.

AU - Balog, Joan Z.

AU - Hadley, Donald W.

AU - Zhou, Nan

AU - Pineda-Alvarez, Daniel E.

AU - Roessler, Erich

AU - Muenke, Maximilian

PY - 2012/7

Y1 - 2012/7

N2 - Background Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of nonchromosomal HPE. The severity spectrum is wide, ranging from incompatibility with extrauterine life to isolated midline facial differences. Objective To characterise genetic and clinical findings in individuals with SHH mutations. Methods Through the National Institutes of Health and collaborating centres, DNA from approximately 2000 individuals with HPE spectrum disorders were analysed for SHH variations. Clinical details were examined and combined with published cases. Results This study describes 396 individuals, representing 157 unrelated kindreds, with SHH mutations; 141 (36%) have not been previously reported. SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (p

AB - Background Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of nonchromosomal HPE. The severity spectrum is wide, ranging from incompatibility with extrauterine life to isolated midline facial differences. Objective To characterise genetic and clinical findings in individuals with SHH mutations. Methods Through the National Institutes of Health and collaborating centres, DNA from approximately 2000 individuals with HPE spectrum disorders were analysed for SHH variations. Clinical details were examined and combined with published cases. Results This study describes 396 individuals, representing 157 unrelated kindreds, with SHH mutations; 141 (36%) have not been previously reported. SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (p

U2 - 10.1136/jmedgenet-2012-101008

DO - 10.1136/jmedgenet-2012-101008

M3 - Article

SN - 0022-2593

VL - 49

SP - 473

EP - 479

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 7

ER -