X-linked mild non-syndromic mental retardation with neuropsychiatric problems and the missense mutation A365E in PAK3

Agi Kyra Gedeon, John Nelson, Jozef Gécz, John C Mulley

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

We describe a family of 19 males in five generations with mild to borderline non-syndromic X-linked mental retardation (MRX). There were no clinical manifestations in the affected males other than mental impairment and relatively long ears, with neuropsychiatric problems in some cases. Linkage analysis carried out on part of the pedigree using 34 markers spanning the X chromosome localized the gene between DXS454 and DXS1001 in Xq23. The maximum two-point lod score was 3.21 at DXS1059. PAK3 is a known MRX gene mapping to the same region. The affected males and obligate carrier females were found to have a missense mutation c.1094C > A in exon 10 causing an A365E substitution in a highly conserved region of the protein. The C to A base change abolishes a PvuII restriction enzyme site providing the basis for a simple test, if required, for carrier detection and prenatal diagnosis in the extended family.

Original languageEnglish
Pages (from-to)509-17
Number of pages9
JournalAm J Med Genet A
Volume120A
Issue number4
DOIs
Publication statusPublished - 1 Aug 2003
Externally publishedYes

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Missense Mutation
Intellectual Disability
X-Linked Mental Retardation
Lod Score
X-Linked Genes
Chromosome Mapping
Pedigree
Prenatal Diagnosis
Ear
Exons
Enzymes
Proteins

Bibliographical note

Copyright 2003 Wiley-Liss, Inc.

Cite this

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abstract = "We describe a family of 19 males in five generations with mild to borderline non-syndromic X-linked mental retardation (MRX). There were no clinical manifestations in the affected males other than mental impairment and relatively long ears, with neuropsychiatric problems in some cases. Linkage analysis carried out on part of the pedigree using 34 markers spanning the X chromosome localized the gene between DXS454 and DXS1001 in Xq23. The maximum two-point lod score was 3.21 at DXS1059. PAK3 is a known MRX gene mapping to the same region. The affected males and obligate carrier females were found to have a missense mutation c.1094C > A in exon 10 causing an A365E substitution in a highly conserved region of the protein. The C to A base change abolishes a PvuII restriction enzyme site providing the basis for a simple test, if required, for carrier detection and prenatal diagnosis in the extended family.",
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X-linked mild non-syndromic mental retardation with neuropsychiatric problems and the missense mutation A365E in PAK3. / Gedeon, Agi Kyra; Nelson, John; Gécz, Jozef; Mulley, John C.

In: Am J Med Genet A, Vol. 120A, No. 4, 01.08.2003, p. 509-17.

Research output: Contribution to journalArticle

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