SLC13A5 is the second gene associated with Kohlschütter-Tönz syndrome

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

Research output: Contribution to journalArticle

Abstract

Background Kohlschütter-Tönz syndrome (KTZS) is a rare autosomal-recessive disease characterised by epileptic encephalopathy, intellectual disability and amelogenesis imperfecta (AI). It is frequently caused by biallelic mutations in ROGDI. Here, we report on individuals with ROGDI-negative KTZS carrying biallelic SLC13A5 mutations. Methods In the present cohort study, nine individuals from four families with the clinical diagnosis of KTZS and absence of ROGDI mutations as well as one patient with unexplained epileptic encephalopathy were investigated by clinical and dental evaluation, parametric linkage analysis (one family), and exome and/or Sanger sequencing. Dental histological investigations were performed on teeth from individuals with SLC13A5- associated and ROGDI-associated KTZS. Results Biallelic mutations in SLC13A5 were identified in 10 affected individuals. Epileptic encephalopathy usually presents in the neonatal and (less frequently) early infantile period. Yellowish to orange discolouration of both deciduous and permanent teeth, as well as wide interdental spaces and abnormal crown forms are major clinical signs of individuals with biallelic SLC13A5 mutations. Histological dental investigations confirmed the clinical diagnosis of hypoplastic AI. In comparison, the histological evaluation of a molar assessed from an individual with ROGDI-associated KTZS revealed hypocalcified AI. Conclusions We conclude that SLC13A5 is the second major gene associated with the clinical diagnosis of KTZS, characterised by neonatal epileptic encephalopathy and hypoplastic AI. Careful clinical and dental delineation provides clues whether ROGDI or SLC13A5 is the causative gene. Hypersensitivity of teeth as well as high caries risk requires individual dental prophylaxis and attentive dental management.

Original languageEnglish (US)
JournalJournal of Medical Genetics
DOIs
StateAccepted/In press - Sep 6 2016

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Tooth
Brain Diseases
Genes
Amelogenesis Imperfecta
Mutation
Dental Prophylaxis
Exome
Deciduous Tooth
Crowns
Intellectual Disability
Hypersensitivity
Cohort Studies
Amelogenesis imperfecta local hypoplastic form

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Schossig, A., Bloch-Zupan, A., Lussi, A., Wolf, N. I., Raskin, S., Cohen, M., ... Kapferer-Seebacher, I. (Accepted/In press). SLC13A5 is the second gene associated with Kohlschütter-Tönz syndrome. Journal of Medical Genetics. https://doi.org/10.1136/jmedgenet-2016-103988

SLC13A5 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; Krabichler, Birgit; Koolen, David A.; Sobreira, Nara; Maurer, Elisabeth; Muller-Bolla, Michèle; Penzien, Johann; Zschocke, Johannes; Kapferer-Seebacher, Ines.

In: Journal of Medical Genetics, 06.09.2016.

Research output: Contribution to journalArticle

Schossig, A, Bloch-Zupan, A, Lussi, A, Wolf, NI, Raskin, S, Cohen, M, Giuliano, F, Jurgens, J, Krabichler, B, Koolen, DA, Sobreira, N, Maurer, E, Muller-Bolla, M, Penzien, J, Zschocke, J & Kapferer-Seebacher, I 2016, 'SLC13A5 is the second gene associated with Kohlschütter-Tönz syndrome', Journal of Medical Genetics. https://doi.org/10.1136/jmedgenet-2016-103988
Schossig, Anna ; Bloch-Zupan, Agnès ; Lussi, Adrian ; Wolf, Nicole I. ; Raskin, Salmo ; Cohen, Monika ; Giuliano, Fabienne ; Jurgens, Julie ; Krabichler, Birgit ; Koolen, David A. ; Sobreira, Nara ; Maurer, Elisabeth ; Muller-Bolla, Michèle ; Penzien, Johann ; Zschocke, Johannes ; Kapferer-Seebacher, Ines. / SLC13A5 is the second gene associated with Kohlschütter-Tönz syndrome. In: Journal of Medical Genetics. 2016.
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abstract = "Background Kohlsch{\"u}tter-T{\"o}nz syndrome (KTZS) is a rare autosomal-recessive disease characterised by epileptic encephalopathy, intellectual disability and amelogenesis imperfecta (AI). It is frequently caused by biallelic mutations in ROGDI. Here, we report on individuals with ROGDI-negative KTZS carrying biallelic SLC13A5 mutations. Methods In the present cohort study, nine individuals from four families with the clinical diagnosis of KTZS and absence of ROGDI mutations as well as one patient with unexplained epileptic encephalopathy were investigated by clinical and dental evaluation, parametric linkage analysis (one family), and exome and/or Sanger sequencing. Dental histological investigations were performed on teeth from individuals with SLC13A5- associated and ROGDI-associated KTZS. Results Biallelic mutations in SLC13A5 were identified in 10 affected individuals. Epileptic encephalopathy usually presents in the neonatal and (less frequently) early infantile period. Yellowish to orange discolouration of both deciduous and permanent teeth, as well as wide interdental spaces and abnormal crown forms are major clinical signs of individuals with biallelic SLC13A5 mutations. Histological dental investigations confirmed the clinical diagnosis of hypoplastic AI. In comparison, the histological evaluation of a molar assessed from an individual with ROGDI-associated KTZS revealed hypocalcified AI. Conclusions We conclude that SLC13A5 is the second major gene associated with the clinical diagnosis of KTZS, characterised by neonatal epileptic encephalopathy and hypoplastic AI. Careful clinical and dental delineation provides clues whether ROGDI or SLC13A5 is the causative gene. Hypersensitivity of teeth as well as high caries risk requires individual dental prophylaxis and attentive dental management.",
author = "Anna Schossig and Agn{\`e}s Bloch-Zupan and Adrian Lussi and Wolf, {Nicole I.} and Salmo Raskin and Monika Cohen and Fabienne Giuliano and Julie Jurgens and Birgit Krabichler and Koolen, {David A.} and Nara Sobreira and Elisabeth Maurer and Mich{\`e}le Muller-Bolla and Johann Penzien and Johannes Zschocke and Ines Kapferer-Seebacher",
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T1 - SLC13A5 is the second gene associated with Kohlschütter-Tönz syndrome

AU - Schossig, Anna

AU - Bloch-Zupan, Agnès

AU - Lussi, Adrian

AU - Wolf, Nicole I.

AU - Raskin, Salmo

AU - Cohen, Monika

AU - Giuliano, Fabienne

AU - Jurgens, Julie

AU - Krabichler, Birgit

AU - Koolen, David A.

AU - Sobreira, Nara

AU - Maurer, Elisabeth

AU - Muller-Bolla, Michèle

AU - Penzien, Johann

AU - Zschocke, Johannes

AU - Kapferer-Seebacher, Ines

PY - 2016/9/6

Y1 - 2016/9/6

N2 - Background Kohlschütter-Tönz syndrome (KTZS) is a rare autosomal-recessive disease characterised by epileptic encephalopathy, intellectual disability and amelogenesis imperfecta (AI). It is frequently caused by biallelic mutations in ROGDI. Here, we report on individuals with ROGDI-negative KTZS carrying biallelic SLC13A5 mutations. Methods In the present cohort study, nine individuals from four families with the clinical diagnosis of KTZS and absence of ROGDI mutations as well as one patient with unexplained epileptic encephalopathy were investigated by clinical and dental evaluation, parametric linkage analysis (one family), and exome and/or Sanger sequencing. Dental histological investigations were performed on teeth from individuals with SLC13A5- associated and ROGDI-associated KTZS. Results Biallelic mutations in SLC13A5 were identified in 10 affected individuals. Epileptic encephalopathy usually presents in the neonatal and (less frequently) early infantile period. Yellowish to orange discolouration of both deciduous and permanent teeth, as well as wide interdental spaces and abnormal crown forms are major clinical signs of individuals with biallelic SLC13A5 mutations. Histological dental investigations confirmed the clinical diagnosis of hypoplastic AI. In comparison, the histological evaluation of a molar assessed from an individual with ROGDI-associated KTZS revealed hypocalcified AI. Conclusions We conclude that SLC13A5 is the second major gene associated with the clinical diagnosis of KTZS, characterised by neonatal epileptic encephalopathy and hypoplastic AI. Careful clinical and dental delineation provides clues whether ROGDI or SLC13A5 is the causative gene. Hypersensitivity of teeth as well as high caries risk requires individual dental prophylaxis and attentive dental management.

AB - Background Kohlschütter-Tönz syndrome (KTZS) is a rare autosomal-recessive disease characterised by epileptic encephalopathy, intellectual disability and amelogenesis imperfecta (AI). It is frequently caused by biallelic mutations in ROGDI. Here, we report on individuals with ROGDI-negative KTZS carrying biallelic SLC13A5 mutations. Methods In the present cohort study, nine individuals from four families with the clinical diagnosis of KTZS and absence of ROGDI mutations as well as one patient with unexplained epileptic encephalopathy were investigated by clinical and dental evaluation, parametric linkage analysis (one family), and exome and/or Sanger sequencing. Dental histological investigations were performed on teeth from individuals with SLC13A5- associated and ROGDI-associated KTZS. Results Biallelic mutations in SLC13A5 were identified in 10 affected individuals. Epileptic encephalopathy usually presents in the neonatal and (less frequently) early infantile period. Yellowish to orange discolouration of both deciduous and permanent teeth, as well as wide interdental spaces and abnormal crown forms are major clinical signs of individuals with biallelic SLC13A5 mutations. Histological dental investigations confirmed the clinical diagnosis of hypoplastic AI. In comparison, the histological evaluation of a molar assessed from an individual with ROGDI-associated KTZS revealed hypocalcified AI. Conclusions We conclude that SLC13A5 is the second major gene associated with the clinical diagnosis of KTZS, characterised by neonatal epileptic encephalopathy and hypoplastic AI. Careful clinical and dental delineation provides clues whether ROGDI or SLC13A5 is the causative gene. Hypersensitivity of teeth as well as high caries risk requires individual dental prophylaxis and attentive dental management.

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