Homozygosity for TNSALP mutation 1348c>T (Arg433Cys) causes infantile hypophosphatasia manifesting transient disease correction and variably lethal outcome in a kindred of black ancestry - 10/08/11
, Kevan Essmyer, MS, Michael Geimer, BS, Steven Mumm, PhD
Reprint requests: Michael P. Whyte, MD, Shriners Hospital for Children, 2001 S Lindbergh Blvd, St. Louis, MO 63131Résumé |
Objective |
To determine the “tissue-nonspecific” isoenzyme of alkaline phosphatase (TNSALP) defect underlying transiently reversible and variably lethal infantile hypophosphatasia (HPP) in a kindred and to characterize HPP prevalence in black people.
Study design |
In 1986, we reported temporary correction of severe HPP in an American kindred of black ancestry where “infantile” HPP was fatal in 2 of 3 affected individuals representing 2 sibships. This transient improvement in 1 patient followed efforts to increase TNSALP activity endogenously and suggested dysregulation of the gene (TNSALP). Here, we sequenced the coding exons and splice sites of the kindred’s TNSALP alleles and reviewed our 30-year experience with HPP to assess its prevalence in black people.
Results |
Homozygosity for TNSALP missense mutation 1348C>T (Arg433Cys) accounted for this kindred’s infantile HPP. The TNSALP promoter sequence was normal. Modeling of TNSALP(433Cys) suggested compromise of the catalytic site. Ethnicity was identified for the 119 families with HPP studied in St. Louis, and race was ascertained for an additional 159 of our 235 consultand HPP families worldwide. In this experience, only this family was of black ancestry.
Conclusions |
Infantile HPP from homozygous TNSALP(433Cys) can remit and thus harbor clues regarding the phenotypic variation and perhaps treatment of HPP.
Le texte complet de cet article est disponible en PDF.Abbreviations : HPP, PCR, PPi, PTH, TNSALP
Plan
| Supported by Shriners Hospitals For Children, The Clark And Mildred Cox Inherited Metabolic Bone Disease Research Fund, The Hypophosphatasia Research Fund, and The Barnes-Jewish Hospital Foundation. |
Vol 148 - N° 6
P. 753-758 - juin 2006 Retour au numéro
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