Syndromic form of X-linked mental retardation with marked hypotonia in early life, severe mental handicap, and difficult adult behavior maps to Xp22.
An X-linked recessive syndromic form of mental retardation is described in a family in which 10 males in four generations were affected. The main manifestations were severe to profound intellectual disability, muscular hypotonia in childhood, delayed walking, and difficult, aggressive behavior. There was a moderate reduction both in occipitofrontal circumference (OFC) and height and a similar facial appearance, triangular in shape with a high forehead, prominent ears, and a small pointed chin. Linkage analysis located the gene at Xp22 with maximum lod scores of 4.8 at theta = 0.0 for markers mapping between the closest recombination points at DXS7104 and DXS418. The physical length of this region is approximately 6 Mb. Mutations in the GRPR gene and M6b genes were excluded by sequence analysis. Nearby genes in which mutations are known to be associated with mental retardation (RPS6KA3, STK9, and VCXA, B and C), were excluded by position.
Turner
Gillian
G
Hunter Genetics, University of Newcastle, PO Box 84, Waratah, New South Wales 2298, Australia. parturn@ozemail.com.au
Gedeon
Agi
A
Kerr
Bronwyn
B
Bennett
Rachael
R
Mulley
John
J
Partington
Michael
M
D000367:Age Factors; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D001523:Mental Disorders / Q000150:complications*; D038901:X-Linked Intellectual Disability / Q000150:complications / Q000235:genetics*; D018895:Microsatellite Repeats; D009123:Muscle Hypotonia / Q000150:complications*; D010375:Pedigree; D012737:Sex Factors