HFG HOXA13-III

Hand-foot-genital syndrome (HFGS) is a very rare multiple congenital abnormality syndrome characterized by distal limb malformations and urogenital defects¹.

Prevalence

Extremely rare, published cases generally European ancestry or unknown^2,3,4.

Age of Onset Details

0 (birth)

Locus

hg19

chr7:27239297-27239351

hg38

chr7:27199678-27199732

t2t

chr7:27335815-27335849

Details

Anticipation does not occur, and expansions appear fully penetrant; it is unknown if contractions also lead to phenotypic variation⁴.

Mechanism

LoF

Polyalanine expansions leading to haploinsufficiency⁴

Year

2000⁵

Location in Gene

Exon 1

Gene Strand

Alleles

Ref. Motif

NGC

Pathogenic (ref.)

NGC

Pathogenic (gene)

CNG

gnomAD

Pathogenic genotype frequency data is not displayed for this locus because a substantial number of large alleles failed manual review by the gnomAD team.

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0007698

Polyalanine expansion in HOXA13: three new affected families and the molecular consequences in a mouse model.

Jeffrey W,Innis, Douglas,Mortlock, Zhi,Chen, Michael,Ludwig, Melissa E,Williams, Thomas M,Williams, Colleen D,Doyle, Zhihong,Shao, Michael,Glynn, Davor,Mikulic, Katarina,Lehmann, Stefan,Mundlos, Boris,Utsch

Human molecular genetics · 2004-09-22

pmid:15385446

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

Hand-Foot-Genital Syndrome

Jeffrey W.,Innis

GeneReviews® · 1993-01-01

genereviews:NBK1423

Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome.

F R,Goodman, C,Bacchelli, A F,Brady, L A,Brueton, J P,Fryns, D P,Mortlock, J W,Innis, L B,Holmes, A E,Donnenfeld, M,Feingold, F A,Beemer, R C,Hennekam, P J,Scambler

American journal of human genetics · 2000-06-05

pmid:10839976

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)

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

Analysis of de novo HOXA13 polyalanine expansions supports replication slippage without repair in their generation.

Kailey M,Owens, Shane C,Quinonez, Peedikayil E,Thomas, Catherine E,Keegan, Nanci,Lefebvre, Diane,Roulston, Christine A,Larsen, H Scott,Stadler, Jeffrey W,Innis

American journal of medical genetics. Part A · 2013-03-26

pmid:23532960

A novel mutation of HOXA13 in a family with hand-foot-genital syndrome and the role of polyalanine expansions in the spectrum of Müllerian fusion anomalies.

Elisa M,Jorgensen, Jane I,Ruman, Leo,Doherty, Hugh S,Taylor

Fertility and sterility · 2009-07-09

pmid:19591980

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

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