[Fine mapping of Smith-Fineman-Myers syndrome and exclusion of GPC3, GPCR2  MST4 and GLUD2 as candidate genes].
OBJECTIVE
Smith-Fineman-Myers syndrome (SFMS) is an X-linked mental retardation syndrome. The authors had ascertained a large Chinese family with SFMS from Shandong and had mapped the disease locus to an interval of 19.8 Mb on Xq25 flanked by markers DXS8064 and DXS8050. Further investigation suggested that SFMS exhibited locus heterogeneity. In this study for facilitating the identification of the gene responsible for SFMS, the additional markers were analyzed to narrow down the candidate region, and four candidate genes (GPC3, MST4,GPCR2 and GLUD2) were chosen and screened for disease-causing mutation.


METHODS
PCR and denaturing polyacrylamide gel electrophoresis were used to genotype 13 new polymorphic markers distributed within the candidate region. Mutation detection was accomplished by sequencing the exons and intron-exon junctions of the candidate genes.


RESULTS
By analyzing 13 additional polymorphic markers, SFMS candidate region can be reduced to an interval of 10.18 Mb bounded by XSTR3 and XSTR4, and no disease-causing mutation was identified in the coding regions of four candidate genes.


CONCLUSIONS
GPCR2  GPC3, MST4 and GLUD2 were excluded as pathogenic genes for SFMS. The refined SFMS locus will assist in the identification and characterization of other candidate genes for SFMS.
Liu
Qi-ji
QJ
Institute of Medical Genetics, School of Medicine, Shandong University, Jinan, Shandong, 250012 PR China.
Gong
Yao-qin
YQ
Li
Jiang-xia
JX
Zhang
Xi-yu
XY
Gao
Gui-min
GM
Guo
Yi-shou
YS
D000015:Abnormalities, Multiple / Q000235:genetics*; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D008040:Genetic Linkage; D005969:Glutamate Dehydrogenase / Q000235:genetics*; D053673:Glypicans; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D013577:Syndrome; D000099317:Hippo Kinases
D005969:Glutamate Dehydrogenase; D053673:Glypicans; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D043562:Receptors, G-Protein-Coupled; C105937:GPC3 protein, human; C430908:STK26 protein, human; D000099317:Hippo Kinases