X‐linked mental retardation with dystonic movements of the hands

Partington, M. W.; Mulley, John C.; Sutherland, G. R.; Hockey, Athel; Thode, Anna B.; Turner, Gillian

doi:10.1002/ajmg.1320300127

Cited by 56 publications

(35 citation statements)

References 5 publications

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“…In the most severe form, ARX related oral dystonia makes part of Partington syndrome (MIM 309510), that combines hand dystonia and ataxia. 16,17 In conclusion, our data further confirm that mentally retarded male subjects with PAK3 mutations share some common clinical and behavioural symptoms. The emerging PAK3-related phenotypes include small head size or microcephaly, oral motor dysfunction with persistent drooling and inarticulate speech, and behavioural and psychiatric symptoms.…”

Section: Discussionsupporting

confidence: 81%

A novel splice mutation in PAK3 gene underlying mental retardation with neuropsychiatric features

et al. 2008

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PAK3-related mental retardation represents a rare cause of X-linked mental retardation associated with behavioural symptoms. So far, four families carrying PAK3 mutations have been reported, and in most cases PAK3 dysfunction resulted from missense mutations thought to affect either the catalytic or the N-terminal regulatory domain activity. Here, we report on a Tunisian family of X-linked moderate mental retardation with behavioural symptoms, common dysmorphic features, oro-motor impairment and secondary microcephaly. Linkage analysis showed that affected male subjects and obligate carrier female subjects share a common haplotype in the Xp21.31 -Xq23 region that contains the PAK3 gene. Direct sequencing of PAK3 coding exons and flanking intronic sequences allowed us to identify the first splice mutation in PAK3 gene located at the 5 0 end of intron 6 (c.276 þ 4A4G), which results in a complete switch-off of the genuine donor splice site and an activation of a cryptic donor splice site (GTAAG) located four nucleotides downstream to the genuine one. RT-PCR experiments using the RNA from the patient's lymphoblasts showed that PAK3 transcripts contain four additional nucleotides that lead to a disruption of reading frame with a premature stop codon at position 128. Together with previously reported observations, our data further confirm that PAK3 mutations result in a specific form of X-linked mental retardation with fairly constant clinical features.

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Section: Discussionsupporting

confidence: 81%

A novel splice mutation in PAK3 gene underlying mental retardation with neuropsychiatric features

et al. 2008

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“…Thus Partington syndrome (PRTS), 15,16 MRXS1, has been assigned to a region of Xp (Xpter-p21) that overlaps with the MEHMO locus critical region. Similar to MEHMO, MR and seizures are characteristic of PRTS.…”

Section: Discussionmentioning

confidence: 99%

MEHMO (mental retardation, epileptic seizures, hypogonadism and -genitalism, microcephaly, obesity), a novel syndrome: assignment of disease locus to Xp21.1–p22.13

1998

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A previously unrecognised X-chromosomal mental retardation syndrome is described. Clinical hallmarks are mental retardation, epileptic seizures, hypogonadism, and -genitalism, microcephaly and obesity. Life expectancy of patients is less than two years. Based on the major clinical symptoms this condition is referred to by the acronym MEHMO. Haplotype and two-point linkage analyses in a large three-generation family assign the disease locus to Xp21.1-p22.13, to a region that is flanked by CYBB and DXS365.

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“…Phenotypes included familial nonsyndromic X-linked mental retardation, 5,9 X-linked infantile spasms (ISSX), 9,17,18 familial mental retardation with hypsarrhythmia, 9 and Partington syndrome. 7,19,20 The latter syndrome is characterized by mild to moderate mental retardation in boys, of which about 60% also have episodic dystonic movements of the hands, which become more prominent in childhood. 7,19,20 Mild dystonia was also reported in some members of two additional families with syndromic and nonsyndromic X-linked mental retardation, and the c.428_451dup mutation.…”

mentioning

confidence: 98%

“…7,19,20 The latter syndrome is characterized by mild to moderate mental retardation in boys, of which about 60% also have episodic dystonic movements of the hands, which become more prominent in childhood. 7,19,20 Mild dystonia was also reported in some members of two additional families with syndromic and nonsyndromic X-linked mental retardation, and the c.428_451dup mutation. 10 Altogether, dystonia has never comprised a severe clinical feature in patients with expansion of the second PolyA tract.…”

mentioning

confidence: 98%

Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus

Guerrini¹,

Moro²,

Kato³

et al. 2007

Neurology

139

118

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X‐linked mental retardation with dystonic movements of the hands

Abstract: We describe a family with a syndrome of mental retardation, dystonic movements of the hands and dysarthria inherited in an X-linked recessive pattern. DNA marker studies gave a maximum lod score of 2.11 at theta of 0.00 for DXS41 with a likely localization of the gene to Xpter----Xp21.

Cited by 56 publications

References 5 publications

A novel splice mutation in PAK3 gene underlying mental retardation with neuropsychiatric features

A novel splice mutation in PAK3 gene underlying mental retardation with neuropsychiatric features

MEHMO (mental retardation, epileptic seizures, hypogonadism and -genitalism, microcephaly, obesity), a novel syndrome: assignment of disease locus to Xp21.1–p22.13

Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus

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