Refined FISH characterization of a de novo 1p22-p36.2 paracentric inversion and associated 1p21-22 deletion in a patient with signs of 1p36 microdeletion syndrome

Abstract

We report on a 10-year-old boy presenting with obesity, moderate mental retardation, large anterior fontanelle at birth, mild physical anomalies including mid-face hypoplasia, deep-set eyes, long philtrum, and small mouth. He was found to carry a paracentric inversion inv(1)(p22p36.2) associated with a 10 cM deletion at the proximal breakpoint. By YAC FISH, the boundaries of the deletion were established at IB1028 (1p21) and WI-5166 (1p22) STSs contained in YACs 781E8 and 954F6, respectively. This large region, covering about 10 cM, contains the COL11A1 and AMY2B genes, whose haploinsufficiency does not seem to contribute significantly to the clinical phenotype. On the other hand, the patient's clinical manifestations, also including visual problems and moderate mental retardation, are those typically observed in the 1p36 deletion syndrome. Refined mapping of the telomeric 1p36.2 inversion breakpoint was obtained by FISH of a PAC contig constructed to encompass this subinterval of the 1p36 microdeletion syndrome region. PACs 1024B10 and 884E7 were found to span the breakpoint, suggesting that the clinical signs of the 1p36 microdeletion syndrome might be due to disruption of a sequence lying at 1p36.2.