American Journal of Medical Genetics 47:504-511 (1993) - Clinical, Cytogenetic, and Molecular Evidence for an Infant With Smith-Magenis Syndrome Born From a Mother Having a Mosaic 17~11.2~12 Deletion Roberto T. Zori, James R. Lupski, Zhang Heju, Frank Greenberg, James M. Killian, Brian A. Gray, Daniel J. Driscoll, Pragna I. Patel, and Joleen L. Zackowski Division of Genetics, Department of Pediatrics, University of Florida, Gainesville, Florida (R .T.Z., BA.G., D.J.D.); Institute for Molecular Genetics (J.R.L., Z.H., F.G., P.I.P.), Human Genome Center (J.R.L., P.I.P), Department of Pediatrics (J.R.L., F.G.), and Department of Neurology (J.M.K.), Baylor Co22ege of Medicine and Texas Children’s Hospital (J.R.L., F.G.), Houston, Texas, and Department of Pediatrics, Eustern Virginia Medical School, Norfolk, Virginia (J.L.Z.) We describe an infant with del(17) (~11.2~12) whose deleted chromosome was inherited from a mosaic mother. The child had mani- festations consistent with Smith-Magenis syndrome. The mother appeared to be of nor- mal intelligence and she had minimal findings of Smith-Magenis syndrome. Separation of chromosome 17 homologues in somatic cell hybrids and molecular studies confirmed the cytogenetic diagnoses and the fact that the mother was mosaic. Furthermore, molecular analysis demonstrated novel breakpoints in this family, with the deletion extending into and completely encompassing the markers duplicated in Charcot-Marie-Tooth (CMT) disease. Although this Smith-Magenis syn- drome patient is completely deleted for the CMT region, her electrophysiological find- ings are different from those found in CMT. This is the only reported case of Smith- Magenis syndrome with transmission from a partially affected mosaic mother. Transmis- sion of interstitial deletions from mosaic par- ents may be more common than thought; therefore, parental chromosomes should be examined when interstitial deletions are iden- tified. o 1993 Wiley-Liss, Inc. KEY WORDS: Smith-Magenis syndrome, chromosome deletion syn- drome, interstitial deletion, chromosome 17, mosaicism, Charcot-Marie-Tooth dis- ease Received for publication November 30, 1992; revision received April 26, 1993. Address reprint requests to Joleen L. Zackowski, Ph.D., Eastern Virginia Medical School, Division of Cytogenetics, Hofheimer Hall, Room 225, 825 Fairfax Avenue, Norfolk, VA 23507. 0 1993 Wiley-Liss, Inc. INTRODUCTION An interstitial deletion of chromosome band 17~11.2 was first reported in 1982 [Smith et al., 19821. Subse- quent reports have led to delineation of the associated Smith-Magenis syndrome (SMS) [Patil and Bartley, 1984; Smith et al., 1986;Stratton et al., 1986;Lockwood et al., 1988;Hamill et al., 1988;Cabral de Almeida et al., 1989; Colley et al., 1990; Greenberg et al., 19911. Clini- cal findings in this microdeletion syndrome were most recently assessed by Greenberg et al. [19911. The more common physical findings include flat midface, bra- chycephaly, broad nasal bridge, and brachydactyly. Be- havioral and functional manifestations most commonly reported include mental retardation, hyperactivity, short stature, failure to thrive, hoarse deep voice, and ‘‘self-destructive’’ behavior. Molecular analysis indi- cated that most patients were deleted for the same group of 5 17~11.2 DNA markers, thus, defining a region which appears to he critical to SMS [Greenberg et al., 19911. The occurrence of SMS, like that of other microdele- tion syndromes sulch as WAGR (Wilms tumor, aniridia, genital abnormalities, and retardation), Langer-Gie- dion syndrome, Angelman syndrome, Prader- Willi syn- drome, Miller-Dieker syndrome, and DiGeorge syn- drome, has generally been found to be sporadic. We report clinical, cytogenetic, and molecular findings on a family in which an infant with SMS inherited the chro- mosome 17 deletion from a mildly affected mosaic mother. MATERIALS AND METHODS Cjrtogenetic Analysis Chromosomes were prepared from peripheral blood lymphocytes and GTG-banded by the method of Sea- bright [ 1971.1;20 metaphases were counted and analyzed for each subject. Construction and Analysis of Somatic Cell Hybrids Hybrids were constructed as described by Lupski et al. [1991bl using a23, a thymidine kinase-deficient hams-