Mutations in JARID1C are associated with X-linked mental retardation, short stature and hyperreflexia

Fatima E. Abidi, L. Holloway, C. A. Moore, David Weaver, R. J. Simensen, R. E. Stevenson, R. C. Rogers, C. E. Schwartz

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Abstract

Background: Mutations in the JARID1C (Jumonji AT-rich interactive domain 1C) gene were recently associated with X-linked mental retardation (XLMR). Mutations in this gene are reported to be one of the relatively more common causes of XLMR with a frequency of approximately 3% in males with proven or probable XLMR. The JARID1C protein functions as a histone 3 lysine 4 (H3K4) demethylase and is involved in the demethylation of H3K4me3 and H3K4me2. Methods: Mutation analysis of the JARID1C gene was conducted in the following cohorts: probands from 23 XLMR families linked to Xp11.2, 92 males with mental retardation and short stature, and 172 probands from small XLMR families with no linkage information. Results: Four novel mutations consisting of two missense mutations, p.A77T and p.V504M, and two frame shift mutations, p.E468fsX2 and p.R1481fsX9, were identified in males with mental retardation. Two of the mutations, p.V504M and p.E468fsX2, are located in the JmjC domain of the JARID1C gene where no previous mutations have been reported. Additional studies showed that the missense mutation, p.V504M, was a de novo event on the grandpaternal X chromosome of the family. Clinical findings of the nine affected males from the four different families included mental retardation (100%), short stature (55%), hyperreflexia (78%), seizures (33%) and aggressive behaviour (44%). The degree of mental retardation consisted of mild (25%), moderate (12%) and severe (63%). Conclusion: Based on the clinical observations, male patients with mental retardation, short stature and hyperreflexia should be considered candidates for mutations in the JARIDR1C gene.

Original languageEnglish
Pages (from-to)787-793
Number of pages7
JournalJournal of Medical Genetics
Volume45
Issue number12
DOIs
StatePublished - Dec 2008

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Abnormal Reflexes
X-Linked Mental Retardation
Intellectual Disability
Mutation
Genes
Missense Mutation
Frameshift Mutation
X Chromosome
Mental Retardation, X-Linked, with Short Stature
Histones
Lysine
Seizures

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Abidi, F. E., Holloway, L., Moore, C. A., Weaver, D., Simensen, R. J., Stevenson, R. E., ... Schwartz, C. E. (2008). Mutations in JARID1C are associated with X-linked mental retardation, short stature and hyperreflexia. Journal of Medical Genetics, 45(12), 787-793. https://doi.org/10.1136/jmg.2008.058990

Mutations in JARID1C are associated with X-linked mental retardation, short stature and hyperreflexia. / Abidi, Fatima E.; Holloway, L.; Moore, C. A.; Weaver, David; Simensen, R. J.; Stevenson, R. E.; Rogers, R. C.; Schwartz, C. E.

In: Journal of Medical Genetics, Vol. 45, No. 12, 12.2008, p. 787-793.

Research output: Contribution to journalArticle

Abidi, FE, Holloway, L, Moore, CA, Weaver, D, Simensen, RJ, Stevenson, RE, Rogers, RC & Schwartz, CE 2008, 'Mutations in JARID1C are associated with X-linked mental retardation, short stature and hyperreflexia', Journal of Medical Genetics, vol. 45, no. 12, pp. 787-793. https://doi.org/10.1136/jmg.2008.058990
Abidi, Fatima E. ; Holloway, L. ; Moore, C. A. ; Weaver, David ; Simensen, R. J. ; Stevenson, R. E. ; Rogers, R. C. ; Schwartz, C. E. / Mutations in JARID1C are associated with X-linked mental retardation, short stature and hyperreflexia. In: Journal of Medical Genetics. 2008 ; Vol. 45, No. 12. pp. 787-793.
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abstract = "Background: Mutations in the JARID1C (Jumonji AT-rich interactive domain 1C) gene were recently associated with X-linked mental retardation (XLMR). Mutations in this gene are reported to be one of the relatively more common causes of XLMR with a frequency of approximately 3{\%} in males with proven or probable XLMR. The JARID1C protein functions as a histone 3 lysine 4 (H3K4) demethylase and is involved in the demethylation of H3K4me3 and H3K4me2. Methods: Mutation analysis of the JARID1C gene was conducted in the following cohorts: probands from 23 XLMR families linked to Xp11.2, 92 males with mental retardation and short stature, and 172 probands from small XLMR families with no linkage information. Results: Four novel mutations consisting of two missense mutations, p.A77T and p.V504M, and two frame shift mutations, p.E468fsX2 and p.R1481fsX9, were identified in males with mental retardation. Two of the mutations, p.V504M and p.E468fsX2, are located in the JmjC domain of the JARID1C gene where no previous mutations have been reported. Additional studies showed that the missense mutation, p.V504M, was a de novo event on the grandpaternal X chromosome of the family. Clinical findings of the nine affected males from the four different families included mental retardation (100{\%}), short stature (55{\%}), hyperreflexia (78{\%}), seizures (33{\%}) and aggressive behaviour (44{\%}). The degree of mental retardation consisted of mild (25{\%}), moderate (12{\%}) and severe (63{\%}). Conclusion: Based on the clinical observations, male patients with mental retardation, short stature and hyperreflexia should be considered candidates for mutations in the JARIDR1C gene.",
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T1 - Mutations in JARID1C are associated with X-linked mental retardation, short stature and hyperreflexia

AU - Abidi, Fatima E.

AU - Holloway, L.

AU - Moore, C. A.

AU - Weaver, David

AU - Simensen, R. J.

AU - Stevenson, R. E.

AU - Rogers, R. C.

AU - Schwartz, C. E.

PY - 2008/12

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N2 - Background: Mutations in the JARID1C (Jumonji AT-rich interactive domain 1C) gene were recently associated with X-linked mental retardation (XLMR). Mutations in this gene are reported to be one of the relatively more common causes of XLMR with a frequency of approximately 3% in males with proven or probable XLMR. The JARID1C protein functions as a histone 3 lysine 4 (H3K4) demethylase and is involved in the demethylation of H3K4me3 and H3K4me2. Methods: Mutation analysis of the JARID1C gene was conducted in the following cohorts: probands from 23 XLMR families linked to Xp11.2, 92 males with mental retardation and short stature, and 172 probands from small XLMR families with no linkage information. Results: Four novel mutations consisting of two missense mutations, p.A77T and p.V504M, and two frame shift mutations, p.E468fsX2 and p.R1481fsX9, were identified in males with mental retardation. Two of the mutations, p.V504M and p.E468fsX2, are located in the JmjC domain of the JARID1C gene where no previous mutations have been reported. Additional studies showed that the missense mutation, p.V504M, was a de novo event on the grandpaternal X chromosome of the family. Clinical findings of the nine affected males from the four different families included mental retardation (100%), short stature (55%), hyperreflexia (78%), seizures (33%) and aggressive behaviour (44%). The degree of mental retardation consisted of mild (25%), moderate (12%) and severe (63%). Conclusion: Based on the clinical observations, male patients with mental retardation, short stature and hyperreflexia should be considered candidates for mutations in the JARIDR1C gene.

AB - Background: Mutations in the JARID1C (Jumonji AT-rich interactive domain 1C) gene were recently associated with X-linked mental retardation (XLMR). Mutations in this gene are reported to be one of the relatively more common causes of XLMR with a frequency of approximately 3% in males with proven or probable XLMR. The JARID1C protein functions as a histone 3 lysine 4 (H3K4) demethylase and is involved in the demethylation of H3K4me3 and H3K4me2. Methods: Mutation analysis of the JARID1C gene was conducted in the following cohorts: probands from 23 XLMR families linked to Xp11.2, 92 males with mental retardation and short stature, and 172 probands from small XLMR families with no linkage information. Results: Four novel mutations consisting of two missense mutations, p.A77T and p.V504M, and two frame shift mutations, p.E468fsX2 and p.R1481fsX9, were identified in males with mental retardation. Two of the mutations, p.V504M and p.E468fsX2, are located in the JmjC domain of the JARID1C gene where no previous mutations have been reported. Additional studies showed that the missense mutation, p.V504M, was a de novo event on the grandpaternal X chromosome of the family. Clinical findings of the nine affected males from the four different families included mental retardation (100%), short stature (55%), hyperreflexia (78%), seizures (33%) and aggressive behaviour (44%). The degree of mental retardation consisted of mild (25%), moderate (12%) and severe (63%). Conclusion: Based on the clinical observations, male patients with mental retardation, short stature and hyperreflexia should be considered candidates for mutations in the JARIDR1C gene.

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