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Background: Mutations in the JARID1C (Jumonji AT-rich interactive domain 1C) gene were recently associated with X-Iinked 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.Rl48lfsX9, 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 JARID1C gene. [ABSTRACT FROM AUTHOR]

A syndrome of multiple anomalies associated with growth failure and delayed development is described. The facies appear distinctive with globular head, prominence of the eyes, hypertelorism, cleft palate, micrognathia, and abnormal pinnae. Other features include vertebral and costal anomalies, cardiac defects, and a peculiar malformation of the hands. At least five other cases of this condition, all occurring in males, may be found in medical reports. The finding of incomplete expression in three maternal relatives of our patient provides evidence for a genetic cause. [ABSTRACT FROM PUBLISHER]

A male infant, the first-born of twins, with features of Cornealia de Lange syndrome is described. His normal twin was discordnat for 3 of the 14 blood loci tested. Chromosomes from the affected infant appeared normal. Though the aetiological basis for the Cornealia de Lange syndrome remains obscure, most authorities accept genetic rather than environmental causation. The present findings of discordance for Cornelia de Lange syndrome in twins support this view but do not clarify the mode of inheritance. [ABSTRACT FROM PUBLISHER]

Presents an abstract of the article "Prevalence of Mutations in X-linked Mental Retardation Genes in Familial Mental Retardation," by Patrick Tarpey, A. Fryer, J. Gecz, J. Goodship, M. Partington, S. Price, C. Schwartz, R. Stevenson, J. Tolmie, G. Turner, R. Wooster, P.A. Futreal, M.R. Stratton, and F.L. Raymond.

Methods: A large family is described in which mental retardation segregates as an X linked trait. Six affected males in three generations were studied by linkage and clinical examination., Results: Characteristic clinical features include short stature, prominent lower lip, small testes, muscle wasting of the lower legs, kyphosis, joint hyperextensibility, abnormal gait, tremor, and decreased fine motor coordination. Affected subjects also had impaired speech and decreased attention span. A carrier female was mildly affected. A similar disorder was not found on review of our XLMR Database of 124 syndromes. Linkage analysis of 37 markers resulted in a lod score of 2.80 at DXS1212 and 2.76 at DXS425. The limiting markers were DXS424 and DXS1047. Ten of 124 XLMR syndromes and eight of 58 MRX families overlap this region., Conclusions: In summary, this family appears to have a new XLMR syndrome localising to Xq24-q25.