<i>SLC13A5</i>is the second gene associated with Kohlschütter–Tönz syndrome

Schossig, Anna; Bloch‐Zupan, Agnès; Lussi, Adrian; Wolf, Nicole I.; Raskin, Salmo; Cohen, Monika; Giuliano, Fabienne; Jurgens, Julie A; Krabichler, Birgit; Koolen, David A.; Sobreira, Nara; Maurer, Elisabeth; Muller‐Bolla, Michèle; Penzien, Johann; Zschocke, Johannes; Kapferer-Seebacher, Ines

doi:10.1136/jmedgenet-2016-103988

Cited by 50 publications

(88 citation statements)

References 40 publications

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“…A recent study further demonstrated the association of SLC13A5 mutations with Kohlschütter–Tönz syndrome, characterized by epileptic encephalopathy, intellectual disability and amelogenesis imperfecta (AI), hereditary disorders with developmental abnormalities in the quantity and quality of enamel [26, 27]. In the current study, abnormalities in teeth and bone of Slc13a5 deficient ( Slc13a5 -/- ) mice were characterized.…”

Section: Introductionmentioning

confidence: 70%

Defective enamel and bone development in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient mice

et al. 2017

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There has been growing recognition of the essential roles of citrate in biomechanical properties of mineralized tissues, including teeth and bone. However, the sources of citrate in these tissues have not been well defined, and the contribution of citrate to the regulation of odontogenesis and osteogenesis has not been examined. Here, tooth and bone phenotypes were examined in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient C57BL/6 mice at 13 and 32 weeks of age. Slc13a5 deficiency led to defective tooth development, characterized by absence of mature enamel, formation of aberrant enamel matrix, and dysplasia and hyperplasia of the enamel organ epithelium that progressed with age. These abnormalities were associated with fragile teeth with a possible predisposition to tooth abscesses. The lack of mature enamel was consistent with amelogenesis imperfecta. Furthermore, Slc13a5 deficiency led to decreased bone mineral density and impaired bone formation in 13-week-old mice but not in older mice. The findings revealed the potentially important role of citrate and Slc13a5 in the development and function of teeth and bone.

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Section: Introductionmentioning

confidence: 70%

Defective enamel and bone development in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient mice

et al. 2017

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“…Whether the consanguinity of parents has any bearing on disease penetrance is yet another area that remains to be addressed because the severity of clinical presentations may vary as a result of the cumulative effect of detrimental genetic aberrations in different in-bred generations. To address these issues, further clinical and genetic characterizations of patients with KTS by including the SLC13 A5 (SoLute Carrier family 13, subtype 5) gene, which was recently shown to be mutated in patients negative for ROGDI mutations, 12 from ethnically defined patients is necessary.…”

Section: Discussionmentioning

confidence: 99%

A novel ROGDI gene mutation is associated with Kohlschutter-Tonz syndrome

Aswath

Ramakrishnan

Teresa

et al. 2018

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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“…Indeed, according to the report, mutation in the SLC13A5 gene, which encodes a sodium-dependent citrate transporter, might also cause KTS 32 . Moreover, the ROGDI gene is reported to play an important role in tumorigenesis and the cell cycle 19, 33 .…”

Section: Discussionmentioning

confidence: 99%

The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome

Lee

Jeong

Choe

et al. 2017

Sci Rep

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Kohlschutter-Tönz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. Rogdi, an essential protein, is highly conserved across metazoans, and mutations in Rogdi are linked to KTS. However, how certain mutations in Rogdi abolish its physiological functions and cause KTS is not known. In this study, we determined the crystal structure of human Rogdi protein at atomic resolution. Rogdi forms a novel elongated curved structure comprising the α domain, a leucine-zipper-like four-helix bundle, and a characteristic β-sheet domain. Within the α domain, the N-terminal H1 helix (residues 19–45) pairs with the C-terminal H6 helix (residues 252–287) in an antiparallel manner, indicating that the integrity of the four-helix bundle requires both N- and C-terminal residues. The crystal structure, in conjunction with biochemical data, indicates that the α domain might undergo a conformational change and provide a structural platform for protein–protein interactions. Disruption of the four-helix bundle by mutation results in significant destabilization of the structure. This study provides structural insights into how certain mutations in Rogdi affect its structure and cause KTS, which has important implications for the development of pharmaceutical agents against this debilitating neurological disease.

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SLC13A5is the second gene associated with Kohlschütter–Tönz syndrome

Cited by 50 publications

References 40 publications

Defective enamel and bone development in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient mice

Defective enamel and bone development in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient mice

A novel ROGDI gene mutation is associated with Kohlschutter-Tonz syndrome

The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tönz Syndrome

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