American Journal of Medical Genetics 50:296-299 (1994) Protelomeric Sequences Are Deleted in Cases of Short Arm Inverted Duplication of Chromosome 8 John C.K. Barber, Rowena zyxwvuts S. James, Christine Patch, and I. Karen Temple Wessex zyxwvutsrqpo Regional Genetics Laboratory, Salisbury District Hospital,. Salisbury (J.C.K.B., R .S.J.), and zyx Wessa Clinical Genetics Service, Princess Anne Hospital, Southampton (C.P., I.K.T.), United Kingdom We present a patient with a de novo inverted duplication of the short arm of chromosome 8. Molecular analysis confirmed the cytogenetic suspicion of a simultaneous deletion of the tip of the short arm and indicated the maternal origin of the abnormality. This deletion made no detectable contribution to the phenotype of the patient which was comparable to that of previous cases of 8p duplication. Similar investigations of inverted duplica- tions involving other chromosomes may re- veal unexpected deletions with significant phenotypic consequences. zyxwvu 0 1994 Wiley-Liss, Inc. KEY WORDS: chromosome abnormality, chromosome 8, inverted du- plication 8p, terminal dele- tion 8p INTRODUCTION “Mirror” or inverted duplications have a particular fascination for cytogeneticists because of their visual symmetry and uncommon occurrence. Eighteen cases of inverted duplication of the short arm of chromosome 8 have been reported previously [Jensen et al., 1982; Fryns et zyxwvuts al., 1985; Dill et al., 1987; Nevin et al., 1990; Gorinati et al., 1991; Mitchell et al., 19911 and among these, Dill et al. zyxwvutsr [1987] were the first to report an in- verted duplication of chromosome 8 with a simultaneous deletion of the short arm distal to the duplication itself. Since then, Gorinati et al. L19911 have presented cyto- genetic evidence and Mitchell et al. [1991] cytogenetic and molecular evidence for similar concomitant dele- tions. Here we present the cytogenetic, molecular, and phe- notypic findings in a further patient. in whom a duplica- tion-deficiency of 8p was found. Received for publication August 12,1993;revision received Octo- ber 29, 1993. Address reprint requests to Mr. John C.K. Barber, Wessex Re- gional Genetics Laboratory, Salisbury District Hospital, Odstock, Salisbury, Wiltshire SP2, 8BJ, United Kingdom. 0 1994 Wiley-Liss, Inc. CLINICAL REPORT NL (laboratory reference no. 9214754) was born at term with a birth weight of 3.6 kg. At 20 hours she presented with signs of obstruction and required emer- gency surgery for malrotation of the gut. She was slow to thrive and generally hypotonic. A CT scan of the brain showed agenesis of the corpus callosum. She developed a thoracic scoliosis convex to the right. Spine roentgen- ograms documented multiple hemivertebrae from C3 to T4. The other vertebrae appeared normal. Now at the age of 5 years she shows significant devel- opmental delay. She moves by commando crawling and is unable to walk. She has no speech. On examination her weight is on the 10th centile and her head circum- ference on the 75th centile. She has dry curly hair. She has a high nasal bridge and long philtrum (Fig. 1).Her palate is high with a deep central groove. Ears are large and posteriorly angulated with bilateral ear pits. Fingers are long and thin with 5th finger clinodactyly. She has increased tone in both legs with bilateral equinovarus deformity of the feet. The rest of the clinical examination was unremarkable. An abdominal ultrasound study showed a small mesenteric cyst to the left of the midline but other internal organs were normal. CYTOGENETIC AND MOLECULAR FINDINGS An 8p zyxwv + karyotype was reported when the patient was first referred. Subsequently an inverted duplication [inv dup(8)(p23.lp21.1)1 was suggested but the distal region of the duplicated chromosome could not be resolved. Both parental karyotypes were normal. Recently a fur- ther repeat was requested as part of a systematic recall of all patients whose karyotypes contained material of uncertain origin which might be identified by chromo- some painting. Chromosomes were prepared by standard techniques after semi-synchronization with FdU and release with thymidine and a modification of the technique described by Pinkel et al. [1988] was used for chromosome paint- ing. The normal chromosome 8 together with all of the abnormal 8 was painted after hybridization with the Cambio chromosome 8 library indicating that the extra material was of chromosome 8 origin. Subsequent anal- ysis of high-resolution G-banded cells confirmed an in-