OBJECTIVE: To report on the biochemistry and clinical and genetic findings of two siblings, the younger sister presenting with recurrent bone pain of the radius and ulna, and medullary sclerosis, and the older brother with soft tissue calcific deposits (tumoral calcinosis) but who later developed bone pain. Both were found to be hyperphosphaturic. MATERIALS AND METHODS: The index family comprised four individuals (father, mother, brother, sister). The affected siblings were the offspring of a non-consanguineous Indian family of Tamil origin. Bidirectional sequencing was performed on the DNA from the index family and on 160 alleles from a population of 80 unrelated unaffected control individuals of Tamil extraction and 72 alleles from individuals of non-Tamil origin. RESULTS: Two symptomatic siblings were found to harbour previously unreported compound heterozygous missense UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3) mutations in exon 4 c.842A>G and exon 5 c.1097T>G. This sequence variation was not detected in the control DNA. This is the first report of siblings exhibiting stigmata of familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome with documented evidence of autosomal recessive missense GALNT3 mutations. CONCLUSION: The findings from this family add further evidence to the literature that familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are manifestations of the same disease and highlight the importance of appropriate metabolic and genetic investigations.
OBJECTIVE: To report on the biochemistry and clinical and genetic findings of two siblings, the younger sister presenting with recurrent bone pain of the radius and ulna, and medullary sclerosis, and the older brother with soft tissue calcific deposits (tumoral calcinosis) but who later developed bone pain. Both were found to be hyperphosphaturic. MATERIALS AND METHODS: The index family comprised four individuals (father, mother, brother, sister). The affected siblings were the offspring of a non-consanguineous Indian family of Tamil origin. Bidirectional sequencing was performed on the DNA from the index family and on 160 alleles from a population of 80 unrelated unaffected control individuals of Tamil extraction and 72 alleles from individuals of non-Tamil origin. RESULTS: Two symptomatic siblings were found to harbour previously unreported compound heterozygous missense UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3) mutations in exon 4 c.842A>G and exon 5 c.1097T>G. This sequence variation was not detected in the control DNA. This is the first report of siblings exhibiting stigmata of familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome with documented evidence of autosomal recessive missense GALNT3 mutations. CONCLUSION: The findings from this family add further evidence to the literature that familial tumoral calcinosis and hyperostosis-hyperphosphataemia syndrome are manifestations of the same disease and highlight the importance of appropriate metabolic and genetic investigations.
Authors: Shoji Ichikawa; Vincent Guigonis; Erik A Imel; Mélanie Courouble; Sophie Heissat; John D Henley; Andrea H Sorenson; Barbara Petit; Anne Lienhardt; Michael J Econs Journal: J Clin Endocrinol Metab Date: 2007-02-20 Impact factor: 5.958
Authors: M Chakhtoura; M S Ramnitz; N Khoury; G Nemer; N Shabb; A Abchee; A Berberi; M Hourani; M Collins; S Ichikawa; G El Hajj Fuleihan Journal: Osteoporos Int Date: 2018-06-20 Impact factor: 4.507
Authors: Lihao Sun; Lin Zhao; Lianjun Du; Peipei Zhang; Minjia Zhang; Min Li; Tingting Liu; Lei Ye; Bei Tao; Hongyan Zhao; Jianmin Liu; Xiaoyi Ding Journal: Bone Res Date: 2016-11-08 Impact factor: 13.567
Authors: Christopher T Esapa; Rosie A Head; Jeshmi Jeyabalan; Holly Evans; Tertius A Hough; Michael T Cheeseman; Eugene G McNally; Andrew J Carr; Gethin P Thomas; Matthew A Brown; Peter I Croucher; Steve D M Brown; Roger D Cox; Rajesh V Thakker Journal: PLoS One Date: 2012-08-13 Impact factor: 3.240