Sclerosing bone dysplasias with hallmarks of dysosteosclerosis in four patients carrying mutations in SLC29A3 and TCIRG1

被引:18
作者
Howaldt, Antonia [1 ,2 ,3 ,4 ]
Nampoothiri, Sheela [5 ]
Quell, Lisa-Marie [1 ,2 ,3 ,4 ]
Ozden, Ayse [6 ]
Fischer-Zirnsak, Bjoern [1 ,2 ,3 ,4 ]
Collet, Corinne [7 ]
de Vernejoul, Marie-Christine [8 ,9 ,10 ]
Doneray, Hakan [6 ]
Kayserili, Hulya [11 ]
Kornak, Uwe [1 ,2 ,3 ,4 ,12 ,13 ]
机构
[1] Charite Univ Med Berlin, Inst Med Genet & Human Genet, Augustenburger Pl 1, D-13353 Berlin, Germany
[2] Free Univ Berlin, Berlin, Germany
[3] Humboldt Univ, Berlin, Germany
[4] Berlin Inst Hlth, Berlin, Germany
[5] Amrita Inst Med Sci & Res Ctr, Cochin, Kerala, India
[6] Ataturk Univ, Fac Med, Erzurum, Turkey
[7] CHU Paris, Hop Lariboisiere, GH St Louis Lariboisiere F Widal, Serv Biochim & Biol Mol, Paris, France
[8] Hop Lariboisiere, INSERM, U1132, BIOSCAR, F-75010 Paris, France
[9] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France
[10] GH St Louis Lariboisiere Fernand Widal, Serv Rhumatol, Paris, France
[11] Koc Univ, Sch Med KUSOM, Dept Med Genet, Istanbul, Turkey
[12] Max Planck Inst Mol Genet, Berlin, Germany
[13] Charite Univ Med Berlin, Berlin Brandenburg Ctr Regenerat Therapies, Berlin, Germany
关键词
TCIRG1; SLC29A3; Autosomal recessive osteopetrosis; Dysosteosclerosis; Platyspondyly; Next generation sequencing; ALBERS-SCHONBERG-DISEASE; AUTOSOMAL-DOMINANT OSTEOPETROSIS; H SYNDROME; NUCLEOSIDE; SUBUNIT; HENT3; FORM; TRANSPORT;
D O I
10.1016/j.bone.2018.12.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The osteopetroses and related sclerosing bone dysplasias can have a broad range of manifestations. Especially in the milder forms, sandwich vertebrae are an easily recognizable and reliable radiological hallmark. We report on four patients from three families presenting with sandwich vertebrae and platyspondyly. The long bone phenotypes were discordant with one patient showing modeling defects and patchy osteosclerosis, while the second displayed only metaphyseal sclerotic bands, and the third and fourth had extreme metaphyseal flaring with uniform osteosclerosis. Two of the four patients had experienced pathological fractures, two had developmental delay, but none showed cranial nerve damage, hepatosplenomegaly, or bone marrow failure. According to these clinical features the diagnoses ranged between intermediate autosomal recessive osteopetrosis and dysosteosclerosis. After exclusion of mutations in CLCN7 we performed gene panel and exome sequencing. Two novel mutations in SLC29A3 were found in the first two patients. In the third family a TCIRG1 C-terminal frameshift mutation in combination with a mutation at position +4 in intron 2 were detected. Our study adds two cases to the small group of individuals with SLC29A3 mutations diagnosed with dysosteosclerosis, and expands the phenotypic variability. The finding that intermediate autosomal recessive osteopetrosis due to TCIRG1 splice site mutations can also present with platyspondyly further increases the molecular heterogeneity of dysosteosclerosis-like sclerosing bone dysplasias.
引用
收藏
页码:495 / 503
页数:9
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