Synpolydactyly (SPD), or syndactyly type II, is defined as a connection between the middle and ring fingers and fourth and fifth toes, variably associated with postaxial polydactyly in the same digits. Minor local anomalies and various metacarpal or metatarsal abnormalities may be present¹.

Prevalence

Syndactyly is found across dozens of unrelated families worldwide². However, syndactyly-5 specific to STR expansion has been found in 3 individuals³.

Age of Onset

0 (birth)

HPO Terms

–

Association

Mendelian

Locus

hg19 chr2:176957786-176957831

hg38 chr2:176093058-176093103

t2t chr2:176581179-176581224

Details

Benign alleles are highly conserved to be 15 repeats, with disease observed in individuals with 22-23 repeats^4,5as well as in individuals with 8-11 repeats³.

Mechanism

GoF

Polyalanine expansion leading to GoF⁶

Detection

Targeted PCR across exon 1 has detected expansions, and subcloning with Sanger sequencing has characterized them [@pmid:9223304].

Year

1996⁴

Location in Gene

Coding Exon 1

Gene Strand

Alleles

Ref. Motif

GCN

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

GCN

Pathogenic (gene)

CNG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

References

Direct supporting references for info on this page.

1omim:186000

Joining the fingers: a HOXD13 Story.

Nathalie,Brison, Philippe,Debeer, Przemko,Tylzanowski

Developmental dynamics : an official publication of the American Association of Anatomists · 2014-01-01

pmid:24038517

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13.

Y,Muragaki, S,Mundlos, J,Upton, B R,Olsen

Science (New York, N.Y.) · 1996-04-26

pmid:8614804

Eight-alanine duplication in homeobox D13 in a Chinese family with synpolydactyly.

Qian,Xin, Lin,Li, Jiangxia,Li, Rongfang,Qiu, Chenhong,Guo, Yaoqin,Gong, Qiji,Liu

Gene · 2012-03-03

pmid:22406499

Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.

Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman

Nature reviews. Genetics · 2024-03-11

pmid:38467784

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Genome sequencing in families with congenital limb malformations.

Jonas,Elsner, Martin A,Mensah, Manuel,Holtgrewe, Jakob,Hertzberg, Stefania,Bigoni, Andreas,Busche, Marie,Coutelier, Deepthi C,de Silva, Nursel,Elçioglu, Isabel,Filges, Erica,Gerkes, Katta M,Girisha, Luitgard,Graul-Neumann, Aleksander,Jamsheer, Peter,Krawitz, Ingo,Kurth, Susanne,Markus, Andre,Megarbane, André,Reis, Miriam S,Reuter, Daniel,Svoboda, Christopher,Teller, Beyhan,Tuysuz, Seval,Türkmen, Meredith,Wilson, Rixa,Woitschach, Inga,Vater, Almuth,Caliebe, Wiebke,Hülsemann, Denise,Horn, Stefan,Mundlos, Malte,Spielmann

Human genetics · 2021-06-22

pmid:34159400

TLR2/6 signaling promotes the expansion of premalignant hematopoietic stem and progenitor cells in the NUP98-HOXD13 mouse model of MDS.

Darlene A,Monlish, Zev J,Greenberg, Sima T,Bhatt, Kathryn M,Leonard, Molly P,Romine, Qian,Dong, Lauren,Bendesky, Eric J,Duncavage, Jeffrey A,Magee, Laura G,Schuettpelz

Experimental hematology · 2020-07-08

pmid:32652111

Unblending of Transcriptional Condensates in Human Repeat Expansion Disease.

Shaon,Basu, Sebastian D,Mackowiak, Henri,Niskanen, Dora,Knezevic, Vahid,Asimi, Stefanie,Grosswendt, Hylkje,Geertsema, Salaheddine,Ali, Ivana,Jerković, Helge,Ewers, Stefan,Mundlos, Alexander,Meissner, Daniel M,Ibrahim, Denes,Hnisz

Cell · 2020-05-07

pmid:32386547

A NUP98-HOXD13 fusion gene impairs differentiation of B and T lymphocytes and leads to expansion of thymocytes with partial TCRB gene rearrangement.

Chul Won,Choi, Yang Jo,Chung, Christopher,Slape, Peter D,Aplan

Journal of immunology (Baltimore, Md. : 1950) · 2009-10-19

pmid:19841179

Fork stalling and template switching as a mechanism for polyalanine tract expansion affecting the DYC mutant of HOXD13, a new murine model of synpolydactyly.

Olivier,Cocquempot, Véronique,Brault, Charles,Babinet, Yann,Herault

Genetics · 2009-06-22

pmid:19546318

Molecular characterization of HOXA13 polyalanine expansion proteins in hand-foot-genital syndrome.

Boris,Utsch, Colleen D,McCabe, Kenneth,Galbraith, Ricardo,Gonzalez, Mark,Born, Jörg,Dötsch, Michael,Ludwig, Heiko,Reutter, Jeffrey W,Innis

American journal of medical genetics. Part A · 2007-12-15

pmid:17935235

Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13.

P,Debeer, C,Bacchelli, P J,Scambler, L,De Smet, J-P,Fryns, F R,Goodman

Journal of medical genetics · 2002-11-01

pmid:12414828

HOXD13 polyalanine tract expansion in classical synpolydactyly type Vordingborg.

Klaus Wilbrandt,Kjaer, Jess,Hedeboe, Merete,Bugge, Claus,Hansen, Karen,Friis-Henriksen, Maria Baeksted,Vestergaard, Niels,Tommerup, John M,Opitz

American journal of medical genetics · 2002-06-15

pmid:12116248

The mouse Hoxd13(spdh) mutation, a polyalanine expansion similar to human type II synpolydactyly (SPD), disrupts the function but not the expression of other Hoxd genes.

S,Bruneau, K R,Johnson, M,Yamamoto, A,Kuroiwa, D,Duboule

Developmental biology · 2001-09-15

pmid:11543619

Locus SD5 HOXD13

Disease

Locus

Alleles

gnomAD

References

Additional Literature