DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis

被引：369

作者：

Lorenz-Depiereux, Bettina

Bastepe, Murat

Benet-Pages, Anna

Amyere, Mustapha

Wagenstaller, Janine

Mueller-Barth, Ursula

Badenhoop, Klaus

Kaiser, Stephanie M.

Rittmaster, Roger S.

Shlossberg, Alan H.

Olivares, Jose L.

Loris, Cesar

Ramos, Feliciano J.

Glorieux, Francis

Vikkula, Miikka

Juppner, Harald ^{[1
]}

Strom, Tim M.

机构：

[1] GSF, Inst Human Genet, Natl Res Ctr Environm & Hlth, D-85764 Neuherberg, Germany

[2] Harvard Univ, Sch Med, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA

[4] Catholic Univ Louvain, B-1200 Brussels, Belgium

[5] Christian Duve Inst, B-1200 Brussels, Belgium

[6] Med Genet, D-63450 Hanau, Germany

[7] Univ Hosp, Div Endocrinol Diabet & Metab, D-60590 Frankfurt, Germany

[8] Queen Elizabeth 2 Hlth Sci Ctr, Div Endocrinol & Metab, Halifax, NS, Canada

[9] Univ Zaragoza, Fac Med, Univ Hosp Lozano Blesa, Dept Pediat, E-50009 Zaragoza, Spain

[10] Univ Zaragoza, Childrens Hosp Miguel Servet, Serv Nephrol, E-50009 Zaragoza, Spain

[11] Shriners Hosp Children, Genet Unit, Montreal, PQ, Canada

[12] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA

[13] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany

来源：

NATURE GENETICS | 2006年 / 38卷 / 11期

关键词：

D O I：

10.1038/ng1868

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH) 2D levels and suggesting that DMP1 may regulate FGF23 expression.

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页码：1248 / 1250

页数：3

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