Mutations in ANTXR1 Cause GAPO Syndrome

Stránecký, Viktor; Hoischen, Alexander; Hartmannová, Hana; Zaki, Maha S.; Chaudhary, Amit; Zudaire, Enrique; Nosková, Lenka; Barešová, Veronika; Přistoupilová, Anna; Hodaňová, Kateřina; Sovová, Jana; Hůlková, Helena; Piherová, Lenka; Hehir-Kwa, Jayne Y.; Silva, Deepthi de; Senanayake, Manouri P; Farrag, Sameh; Zeman, Jiřı́; Martásek, Pavel; Baxová, A; Afifi, Hanan H.; Croix, Brad St.; Brunner, Han G.; Temtamy, Samia; Kmoch, Stanislav

doi:10.1016/j.ajhg.2013.03.023

Cited by 81 publications

(75 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The craniofacial appearance in GAPO (G, growth retardation; A, alopecia; P, pseudoanodontia; O, optic atrophy) syndrome resembles that of CED [Demirgues et al, 2009]; however, unlike the above mentioned disorders GAPO has recently been found to be caused by defects in extracellular matrix regulation [Stránecký et al, 2013].…”

Section: Differential Diagnosismentioning

confidence: 99%

Sensenbrenner syndrome (Cranioectodermal dysplasia): Clinical and molecular analyses of 39 patients including two new patients

Lin

Traum

Sahai

et al. 2013

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Sensenbrenner syndrome, also known as cranioectodermal dysplasia, is a rare multiple anomaly syndrome with distinctive craniofacial appearance, skeletal, ectodermal, connective tissue, renal, and liver anomalies. Dramatic advances with next‐generation sequencing have expanded its phenotypic variability and molecular heterogeneity. We review 39 patients including two new patients, one with compound heterozygous novel mutations in WDR35 and a previously unreported multisutural craniosynostosis that may be a part of Sensenbrenner syndrome. In 14 of 25 (56.0%) patients pathogenic mutations have been identified in 4 different genes that regulate (intraflagellar) cilia transport. We compared Sensenbrenner syndrome to asphyxiating thoracic dystrophy‐Jeune syndrome (ATD‐JS) and other ciliopathies. Our analyses showed that the high anterior hairline, forehead bossing and dolichocephaly (accompanied by sagittal craniosynostosis in more than half of the patients) occur in almost all patients with Sensenbrenner syndrome. Metaphyseal dysplasia with narrow thorax, proximal limb shortness, and short fingers are typical of Sensenbrenner syndrome and ATD‐JS. Respiratory complications have been reported in both syndromes, usually less severe with Sensenbrenner syndrome. Proposed diagnostic criteria for Sensenbrenner syndrome include the distinctive craniofacial appearance, ubiquitous brachydactyly and ectodermal anomalies, and sagittal craniosynostosis. Mild heart defects have been noted, but there have been no atrioventricular canal or heterotaxy defects that are common in Ellis‐Van Creveld syndrome. We anticipate that the steady identification of molecularly defined patients may allow correlation of phenotype and genotype. Additional natural history data will improve genetic counseling and current guidelines. © 2013 Wiley Periodicals, Inc.

show abstract

Section: Differential Diagnosismentioning

confidence: 99%

Sensenbrenner syndrome (Cranioectodermal dysplasia): Clinical and molecular analyses of 39 patients including two new patients

Lin

Traum

Sahai

et al. 2013

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…In Gorham-Stout disease, characterized by massive osteolysis and hemangiomatosis, VEGF secreted by osteoblasts may induce vascularization, while absence of nuclear VEGF most likely affects osteoblast differentiation [32]. Recent data demonstrated the role of tumor endothelial marker 8 (TEM8) in the pathophysiology of hemangiomas [33] and growth retardation, alopecia, pseudoanodontia, and optic atrophy (GAPO) syndrome [34] through regulation of VEGF signaling in endothelial cells. TEM8 forms a complex with VEGFR2 in endothelial cells and inhibits transcription of VEGFR1, thus protecting the cells from excessive signaling.…”

Section: Vasculature -Olsenmentioning

confidence: 98%

Mechanistic and therapeutic insights gained from studying rare skeletal diseases

Tosi

Warman

2015

Bone

View full text Add to dashboard Cite

Rare bone diseases account for 5% of all birth defects and can cause significant morbidity throughout patients' lives. Significant progress is being made to elucidate the pathophysiological mechanisms underlying these diseases. This paper summarizes presentation highlights of a workshop on Rare Skeletal Diseases convened to explore how the study of rare diseases has influenced the field's understanding of bone anabolism and catabolism and directed the search for new therapies benefiting patients with rare conditions as well as patients with common skeletal disorders.

show abstract

“…While our exome sequencing work was in progress, homozygous mutations in ANTXR1 located on chromosome 2p13.3 were described to be causative for GAPO syndrome [Stranecky et al, 2013]. Immunofluorescence analysis of cultured skin fibroblasts collected from GAPO cases demonstrated an aberrant pattern of actin cytoskeletal microfilament organization.…”

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing identifies three novel mutations in ANTXR1 in families with GAPO syndrome

Bayram

Pehlivan

Karaca

et al. 2014

American J of Med Genetics Pt A

View full text Add to dashboard Cite

GAPO syndrome (OMIM#230740) is the acronym for growth retardation, alopecia, pseudoanodontia, and optic atrophy. About 35 cases have been reported, making it among one of the rarest recessive conditions. Distinctive craniofacial features including alopecia, rarefaction of eyebrows and eyelashes, frontal bossing, high forehead, mid-facial hypoplasia, hypertelorism, and thickened eyelids and lips make GAPO syndrome a clinically recognizable phenotype. While this genomic study was in progress mutations in ANTXR1 were reported to cause GAPO syndrome. In our study we performed whole exome sequencing (WES) for five affected individuals from three Turkish kindreds segregating the GAPO trait. Exome sequencing analysis identified three novel homozygous mutations including; one frame-shift (c.1220_1221insT; p.Ala408Cysfs*2), one splice site (c.411A>G; p.Gln137Gln), and one non-synonymous (c.1150G>A; p.Gly384Ser) mutation in the ANTXR1 gene. Our studies expand the allelic spectrum in this rare condition and potentially provide insight into the role of ANTXR1 in the regulation of the extracellular matrix.

show abstract

Mutations in ANTXR1 Cause GAPO Syndrome

Cited by 81 publications

References 36 publications

Sensenbrenner syndrome (Cranioectodermal dysplasia): Clinical and molecular analyses of 39 patients including two new patients

Sensenbrenner syndrome (Cranioectodermal dysplasia): Clinical and molecular analyses of 39 patients including two new patients

Mechanistic and therapeutic insights gained from studying rare skeletal diseases

Whole exome sequencing identifies three novel mutations in ANTXR1 in families with GAPO syndrome

Contact Info

Product

Resources

About