Mutation in the HPGD gene encoding NAD+ dependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbing (ICNC)

Tariq, Muhammad; Azeem, Zahid; Ali, Ghazanfar; Chishti, Muhammad Salman; Ahmad, Wasim

doi:10.1136/jmg.2008.061234

Cited by 52 publications

(43 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6,7 Recently, a homozygous missense mutation in HPGD has been identified in a single family affected with isolated congenital nail clubbing as an autosomal-recessive trait. 9 In this study, we found significant linkage of COA to a region harboring the HPGD gene in one affected family and report novel mutations in HPGD causing COA in two families. However, in a third family with dominant inheritance of isolated digital nail clubbing, we found no mutation in HPGD indicating another underlying gene defect.…”

Section: Two Variants Of Pho Have Been Distinguished Clinically (Suppmentioning

confidence: 58%

“…7,9,14 Two of four mutations detected so far result in truncation of the HPGD transcript due to nucleotide deletions. 7,9,14 These two mutations alter the open reading frame and result in truncated proteins, which lack the PGD 2 -binding domain. 7 By analyzing the crystal structure of HPGD, the reported homozygous amino-acid substitution Ala140Pro is predicted to disrupt binding of PGE 2 .…”

Section: Discussionmentioning

confidence: 99%

“…7 Another homozygous missense mutation p.S193P is predicted to disrupt the helical structure by reduced stability of the helix number eleven due to introduction of proline residue. 9 The current distribution of mutations shows no putative mutation hotspot region. Taken together the clinical data of the patients with COA reported here, there is marked intrafamilial and interfamilial variability.…”

mentioning

confidence: 96%

“…9 An autosomalrecessive variant has been found to be caused by a missense mutation in HPGD in a consanguineous family from Pakistan. 9,14 Heterozygous individuals of this family have clinically normal fingers and toes. Autosomal dominant digital clubbing (MIM 119900) has been rarely reported and was thought to be distinct from PHO.…”

mentioning

confidence: 99%

See 3 more Smart Citations

HPGD mutations cause cranioosteoarthropathy but not autosomal dominant digital clubbing

Seifert

Beninde²,

Hoffmann

et al. 2009

Eur J Hum Genet

View full text Add to dashboard Cite

Cranio-osteoarthropathy, clinically classified as a variant of primary hypertrophic osteoarthropathy, is a very rare autosomal-recessive condition characterized by delayed closure of the cranial sutures and fontanels, digital clubbing, arthropathy, and periostosis. Recently, mutations in the gene HPGD, which encodes the NAD þ -dependent 15-hydroxyprostaglandin dehydrogenase, were reported in four families affected with primary hypertrophic osteoarthropathy and one family with autosomal-recessive isolated nail clubbing. We report the clinical and molecular findings in four patients from two families affected with cranio-osteoarthropathy and one family with isolated, autosomal dominant digital clubbing. Genomewide homozygosity mapping identified a locus for cranio-osteoarthropathy harboring the HPGD gene in one affected family. We detected two novel homozygous mutations in HPGD in these families: a missense mutation affecting the NAD þ binding motif and a frameshift mutation. The clinical presentation in our patients was variable. Digital clubbing and hyperhidrosis were present in all cases. Delayed closure of the cranial sutures and fontanels, periostosis, and arthropathy were not consistent clinical features. No HPGD mutation was detected in a familial case of autosomal dominant isolated digital clubbing. The failure to identify any mutation in a family with an autosomal dominant type of isolated digital clubbing suggests that HPGD is not the major gene for this condition.

show abstract

Section: Two Variants Of Pho Have Been Distinguished Clinically (Suppmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%

See 2 more Smart Citations

HPGD mutations cause cranioosteoarthropathy but not autosomal dominant digital clubbing

Seifert

Beninde²,

Hoffmann

et al. 2009

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…• периостоз обусловлен PgE2-опосредованной стимуля-цией активности остеобластов и остеокластов за счет повышения VEGF [20]; • пахидермия возникает вследствие чрезмерного синте-за внекостного матрикса фибробластами, обусловлен-ного гиперсекрецией VEGF и фактора роста тромбоци-тов (PDGF) [21]; • утолщение концевых фаланг пальцев происходит за счет увеличения пролиферации фибробластов и пе-риферической вазодилатационной активности PgE2 посредством повышения концентрации PDGF [22]; • задержка постнатального закрытия артериального (Бо-таллова) протока (в 25% случаев при наличии мутации в гене HPGD против 0,5% встречаемости в общей попу-ляции [11,23]) связана с отсутствием быстрого падения циркуляции простагландина Е2 после установления ле-гочного дыхания [11]; • гиперпигментация и утолщение волос и ресниц объяс-няется наличием рецепторов к PgE2 в волосяных фол-ликулах [24];…”

Section: Discussionunclassified

Pachydermoperiostosis: a case report

et al. 2017

View full text Add to dashboard Cite

Pachydermoperiostosis (PHO) or primary hypertrophic osteoarthropathy is a rare genetic disease that typically begins during childhood or adolescence. It is characterized by digital clubbing, pachydermia and periosteal reaction and progresses gradually over the years prior to disease stabilization. Two genes are reported to be associated with PHO – HPGD and SLCO2A1. These genes are involved in prostaglandin E2 metabolism. We present a description of a 19-year-old patient with PHO. We found two mutations in the SLCO2A1 gene: p.Gly183Ar (chr3:133673888, NM_005630.2:c.547G>A) and p.Cys444Gly (chr3:133664070, NM_005630.2:c.1330T>G) through molecular genetic analysis. The mutation (p.Cys444Gly) has never been recorded in previous studies. This work expands our knowledge of the mutation spectrum of PHO, which will facilitate faster genetic diagnosis and interpretation of genetic information in prenatal diagnosis and genetic counseling.

show abstract

Genetics of Isolated Hereditary Nail Disorder

Basit

2017

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Recent advances in molecular genetics and emergence of next‐generation genomic tools have led to the identification of many genes expressed in nail matrix/bed. However, the precise roles of these genes in the nail development and regeneration have not completely been disclosed. Using the methods of forward genetics, a series of genes responsible for hereditary nail disorders have recently been identified. Furthermore, expression and functional analyses have gradually revealed that these genes are directly or indirectly related with each other. This article briefly discusses the clinical and genetic perspective on defining and classifying isolated hereditary nail disorders and the overlapping genetic pathways. The journey towards unravelling the molecular basis of hereditary nail disorders will contribute to better understanding of the complex mechanisms for nail morphogenesis and development in humans. Key Concepts Genetic and non‐genetic factors contribute to nail diseases. Hereditary nail disorders may exist as an isolated entity or associated with other diseases. Underlying genes in nail disorders and signalling pathways in nail development can provide a logical basis for the classification of genetic disorders of nail. To date, mutations in five genes have been identified as a cause of isolated hereditary nail disorders. Development of nail unit requires epithelial–mesenchymal interactions. Wnt signalling pathway is crucial for maintaining epithelial–mesenchymal interaction. Lipid biosynthesis is required for the development and maintenance of proper nail structure.

show abstract

Mutation in the HPGD gene encoding NAD+ dependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbing (ICNC)

Abstract: The involvement of 15-PGDH in the pathogenesis of ICNC may open up interesting perspectives into the function of this enzyme in nail morphogenesis/development.

Cited by 52 publications

References 31 publications

HPGD mutations cause cranioosteoarthropathy but not autosomal dominant digital clubbing

HPGD mutations cause cranioosteoarthropathy but not autosomal dominant digital clubbing

Pachydermoperiostosis: a case report

Genetics of Isolated Hereditary Nail Disorder

Contact Info

Product

Resources

About