A narrow segment of maternal uniparental disomy of chromosome 7q31-qter in Silver-Russell syndrome delimits a candidate gene region.
Maternal uniparental disomy of chromosome 7 (matUPD7), the inheritance of both chromosomes from only the mother, is observed in approximately 10% of patients with Silver-Russell syndrome (SRS). It has been suggested that at least one imprinted gene that regulates growth and development resides on human chromosome 7. To date, three imprinted genes-PEG1/MEST, gamma2-COP, and GRB10-have been identified on chromosome 7, but their role in the etiology of SRS remains uncertain. In a systematic screening with microsatellite markers, for matUPD7 cases among patients with SRS, we identified a patient who had a small segment of matUPD7 and biparental inheritance of the remainder of chromosome 7. Such a pattern may be explained by somatic recombination in the zygote. The matUPD7 segment at 7q31-qter extends for 35 Mb and includes the imprinted gene cluster of PEG1/MEST and gamma2-COP at 7q32. GRB10 at 7p11.2-p12 is located within a region of biparental inheritance. Although partial UPD has previously been reported for chromosomes 6, 11, 14, and 15, this is the first report of a patient with SRS who has segmental matUPD7. Our findings delimit a candidate imprinted region sufficient to cause SRS.
Hannula
K
K
Department of Medical Genetics, Haartman Institute, FIN-00014 University of Helsinki, Finland. katariina.hannula@helsinki.fi
Lipsanen-Nyman
M
M
Kontiokari
T
T
Kere
J
J
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D000782:Aneuploidy; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D020756:Coatomer Protein; D003434:Crossing Over, Genetic / Q000235:genetics; D005220:Fathers; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009035:Mothers; D011506:Proteins / Q000235:genetics; D013577:Syndrome
C485814:COPG2 protein, human; D002352:Carrier Proteins; D020756:Coatomer Protein; D011506:Proteins; C103637:mesoderm specific transcript protein