Synpolydactyly and HOXD13 polyalanine repeat

Addition of 2 alanine residues is without clinical consequences

Sajid Malik, K. M. Girisha, Muhammad Wajid, Akhilesh K. Roy, Shubha R. Phadke, Sayedul Haque, Wasim Ahmad, Manuela C. Koch, Karl Heinz Grzeschik

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Type II syndactyly or synpolydactyly (SPD) is clinically very heterogeneous, and genetically three distinct SPD conditions are known and have been designated as SPD1, SPD2 and SPD3, respectively. SPD1 type is associated with expansion mutations in HOXD13, resulting in an addition of ≥ 7 alanine residues to the polyalanine repeat. It has been suggested that expansions ≤ 6 alanine residues go without medical attention, as no such expansion has ever been reported with the SPD1 phenotype. Methods: We describe a large Pakistani and an Indian family with SPD. We perform detailed clinical and molecular analyses to identify the genetic basis of this malformation. Results: We have identified four distinct clinical categories for the SPD1 phenotype observed in the affected subjects in both families. Next, we show that a milder foot phenotype, previously described as a separate entity, is in fact a part of the SPD1 phenotypic spectrum. Then, we demonstrate that the phenotype in both families segregates with an identical expansion mutation of 21 bp in HOXD13. Finally, we show that the HOXD13 polyalanine repeat is polymorphic, and the expansion of 2 alanine residues, evident in unaffected subjects of both families, is without clinical consequences. Conclusion: It is the first molecular evidence supporting the hypothesis that expansion of ≤ 6 alanine residues in the HOXD13 polyalanine repeat is not associated with the SPD1 phenotype.

Original languageEnglish
Article number78
JournalBMC Medical Genetics
Volume8
DOIs
Publication statusPublished - 11-12-2007

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Alanine
Phenotype
Mutation
Foot
Type 2 Syndactyly
polyalanine

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Genetics(clinical)

Cite this

Malik, Sajid ; Girisha, K. M. ; Wajid, Muhammad ; Roy, Akhilesh K. ; Phadke, Shubha R. ; Haque, Sayedul ; Ahmad, Wasim ; Koch, Manuela C. ; Grzeschik, Karl Heinz. / Synpolydactyly and HOXD13 polyalanine repeat : Addition of 2 alanine residues is without clinical consequences. In: BMC Medical Genetics. 2007 ; Vol. 8.
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abstract = "Background: Type II syndactyly or synpolydactyly (SPD) is clinically very heterogeneous, and genetically three distinct SPD conditions are known and have been designated as SPD1, SPD2 and SPD3, respectively. SPD1 type is associated with expansion mutations in HOXD13, resulting in an addition of ≥ 7 alanine residues to the polyalanine repeat. It has been suggested that expansions ≤ 6 alanine residues go without medical attention, as no such expansion has ever been reported with the SPD1 phenotype. Methods: We describe a large Pakistani and an Indian family with SPD. We perform detailed clinical and molecular analyses to identify the genetic basis of this malformation. Results: We have identified four distinct clinical categories for the SPD1 phenotype observed in the affected subjects in both families. Next, we show that a milder foot phenotype, previously described as a separate entity, is in fact a part of the SPD1 phenotypic spectrum. Then, we demonstrate that the phenotype in both families segregates with an identical expansion mutation of 21 bp in HOXD13. Finally, we show that the HOXD13 polyalanine repeat is polymorphic, and the expansion of 2 alanine residues, evident in unaffected subjects of both families, is without clinical consequences. Conclusion: It is the first molecular evidence supporting the hypothesis that expansion of ≤ 6 alanine residues in the HOXD13 polyalanine repeat is not associated with the SPD1 phenotype.",
author = "Sajid Malik and Girisha, {K. M.} and Muhammad Wajid and Roy, {Akhilesh K.} and Phadke, {Shubha R.} and Sayedul Haque and Wasim Ahmad and Koch, {Manuela C.} and Grzeschik, {Karl Heinz}",
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Synpolydactyly and HOXD13 polyalanine repeat : Addition of 2 alanine residues is without clinical consequences. / Malik, Sajid; Girisha, K. M.; Wajid, Muhammad; Roy, Akhilesh K.; Phadke, Shubha R.; Haque, Sayedul; Ahmad, Wasim; Koch, Manuela C.; Grzeschik, Karl Heinz.

In: BMC Medical Genetics, Vol. 8, 78, 11.12.2007.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synpolydactyly and HOXD13 polyalanine repeat

T2 - Addition of 2 alanine residues is without clinical consequences

AU - Malik, Sajid

AU - Girisha, K. M.

AU - Wajid, Muhammad

AU - Roy, Akhilesh K.

AU - Phadke, Shubha R.

AU - Haque, Sayedul

AU - Ahmad, Wasim

AU - Koch, Manuela C.

AU - Grzeschik, Karl Heinz

PY - 2007/12/11

Y1 - 2007/12/11

N2 - Background: Type II syndactyly or synpolydactyly (SPD) is clinically very heterogeneous, and genetically three distinct SPD conditions are known and have been designated as SPD1, SPD2 and SPD3, respectively. SPD1 type is associated with expansion mutations in HOXD13, resulting in an addition of ≥ 7 alanine residues to the polyalanine repeat. It has been suggested that expansions ≤ 6 alanine residues go without medical attention, as no such expansion has ever been reported with the SPD1 phenotype. Methods: We describe a large Pakistani and an Indian family with SPD. We perform detailed clinical and molecular analyses to identify the genetic basis of this malformation. Results: We have identified four distinct clinical categories for the SPD1 phenotype observed in the affected subjects in both families. Next, we show that a milder foot phenotype, previously described as a separate entity, is in fact a part of the SPD1 phenotypic spectrum. Then, we demonstrate that the phenotype in both families segregates with an identical expansion mutation of 21 bp in HOXD13. Finally, we show that the HOXD13 polyalanine repeat is polymorphic, and the expansion of 2 alanine residues, evident in unaffected subjects of both families, is without clinical consequences. Conclusion: It is the first molecular evidence supporting the hypothesis that expansion of ≤ 6 alanine residues in the HOXD13 polyalanine repeat is not associated with the SPD1 phenotype.

AB - Background: Type II syndactyly or synpolydactyly (SPD) is clinically very heterogeneous, and genetically three distinct SPD conditions are known and have been designated as SPD1, SPD2 and SPD3, respectively. SPD1 type is associated with expansion mutations in HOXD13, resulting in an addition of ≥ 7 alanine residues to the polyalanine repeat. It has been suggested that expansions ≤ 6 alanine residues go without medical attention, as no such expansion has ever been reported with the SPD1 phenotype. Methods: We describe a large Pakistani and an Indian family with SPD. We perform detailed clinical and molecular analyses to identify the genetic basis of this malformation. Results: We have identified four distinct clinical categories for the SPD1 phenotype observed in the affected subjects in both families. Next, we show that a milder foot phenotype, previously described as a separate entity, is in fact a part of the SPD1 phenotypic spectrum. Then, we demonstrate that the phenotype in both families segregates with an identical expansion mutation of 21 bp in HOXD13. Finally, we show that the HOXD13 polyalanine repeat is polymorphic, and the expansion of 2 alanine residues, evident in unaffected subjects of both families, is without clinical consequences. Conclusion: It is the first molecular evidence supporting the hypothesis that expansion of ≤ 6 alanine residues in the HOXD13 polyalanine repeat is not associated with the SPD1 phenotype.

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