Clinical Generics 1991: 4 0 417-422
De novo 13q partial duplication identified by cytogenetic, biochemicaland molecular approaches S.SCHWARTZ', M. HARRIS',R. EHRENPREIS', A. ZASLAV*, L. J. RAFFEL',M. F.SCHWARTZ"', E. LIEBER' AND M. M. COHEN'" 'Division of Human Genetics, Departments of Obstetrics and Gynecology and Pediatrics, University of Maryland School of Medicine. 'Department of Pediatrics, Long Island Jewish Hospital, New York, New York, 'Department of Pediatrics, Patuxent Medical Group, Columbia, Maryland, 4Jewish Hospital of Brooklyn, Brooklyn. New York and 'Medical Biotechnology Center of the Maryland Biotechnology Institute. USA A 3.5-month-old female infant manifesting dysmorphic facies, developmental delay and failure to thrive was referred for cytogenetic evaluation. Peripheral lymphocytes revealed three chromosomally distinct cell lines: 46,XX/46,XX, lop+ /47,XX,lOp+, +mar. Dermal fibroblasts revealed only the 46,M,IOpfcell line. High resolution G-, R-, and Q-banding suggested that the extra chromosomal material (lop+) represented a duplication of the segment 13q14413qter. Parental karyotypes were normal. As absolute identification of de novo chromosomal abnormalities, based solely on cytogenetic studies, is sometimes difficult, both biochemical and molecular approaches were undertaken to elucidate this abnormality in more detail. Dosage effects were examined using esterase D (localized to 13q14.1) and the DNA probes plE8 and p9A7 (localized t o 13q22 and 13q31/32, respectively). These studies suggested the presence of only 2 copies of esterase D, but 3 copies of both DNA probes, allowing identification of the breakpoint at 13q14.2.
Received 8 August 1989, revised 2 February, accepted for publication 24 February 1991 Key words: de novo chromosome abnormality; dosage effects; duplication 13q.
We evaluated an infant manifesting features suggestive of trisomy 13q, a clinically discernible syndrome (Tharapel et al. 1986). Because of the initial difficulties encountered in the cytogenetic identification of the de nova chromosomal abnormality in this patient, more detailed cytogenetic studies were undertaken. Additionally, biochemical and molecular analyses of markers assigned to chromosome 13 were performed (i.e., esterase D [ESDJ,localized to 13q14.1 (Sparkes et al. 1984) and the DNA probes plE8 and p9AI localized to bands 13q22 and 13q31 / 32, respectively (Cavenee et al. 1984; Dryja et al. 1984; Dryja & Morton 1985).
Biochemical studies of the cultured fibroblasts from our patient revealed a normal level of esterase D activity. However, molecular studies did demonstrate a dosage effect for both the plE8 and p9A7 DNA sequences. These findings, along with the cytogenetic studies, suggest a duplication 13ql4.2-13qter in this infant. Case Report
The proband, a 3.5-month-old Caucasian female, was referred for evaluation of multiple congenital anomalies. She was the product of a full-term gestation, born to
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unrelated parents (both aged 24) by normal spontaneous vaginal delivery. The pregnancy was complicated by a viral illness which was treated with antibiotics. Apgar scores were 6' and 9'. Birth weight was 2740 g (3rd-10th percentile), birth length was 45 cm (3rd percentile), and head circumference was 28 cm;
De novo 13q partial duplication identified by cytogenetic, biochemicaland molecular approaches S.SCHWARTZ', M. HARRIS',R. EHRENPREIS', A. ZASLAV*, L. J. RAFFEL',M. F.SCHWARTZ"', E. LIEBER' AND M. M. COHEN'" 'Division of Human Genetics, Departments of Obstetrics and Gynecology and Pediatrics, University of Maryland School of Medicine. 'Department of Pediatrics, Long Island Jewish Hospital, New York, New York, 'Department of Pediatrics, Patuxent Medical Group, Columbia, Maryland, 4Jewish Hospital of Brooklyn, Brooklyn. New York and 'Medical Biotechnology Center of the Maryland Biotechnology Institute. USA A 3.5-month-old female infant manifesting dysmorphic facies, developmental delay and failure to thrive was referred for cytogenetic evaluation. Peripheral lymphocytes revealed three chromosomally distinct cell lines: 46,XX/46,XX, lop+ /47,XX,lOp+, +mar. Dermal fibroblasts revealed only the 46,M,IOpfcell line. High resolution G-, R-, and Q-banding suggested that the extra chromosomal material (lop+) represented a duplication of the segment 13q14413qter. Parental karyotypes were normal. As absolute identification of de novo chromosomal abnormalities, based solely on cytogenetic studies, is sometimes difficult, both biochemical and molecular approaches were undertaken to elucidate this abnormality in more detail. Dosage effects were examined using esterase D (localized to 13q14.1) and the DNA probes plE8 and p9A7 (localized t o 13q22 and 13q31/32, respectively). These studies suggested the presence of only 2 copies of esterase D, but 3 copies of both DNA probes, allowing identification of the breakpoint at 13q14.2.
Received 8 August 1989, revised 2 February, accepted for publication 24 February 1991 Key words: de novo chromosome abnormality; dosage effects; duplication 13q.
We evaluated an infant manifesting features suggestive of trisomy 13q, a clinically discernible syndrome (Tharapel et al. 1986). Because of the initial difficulties encountered in the cytogenetic identification of the de nova chromosomal abnormality in this patient, more detailed cytogenetic studies were undertaken. Additionally, biochemical and molecular analyses of markers assigned to chromosome 13 were performed (i.e., esterase D [ESDJ,localized to 13q14.1 (Sparkes et al. 1984) and the DNA probes plE8 and p9AI localized to bands 13q22 and 13q31 / 32, respectively (Cavenee et al. 1984; Dryja et al. 1984; Dryja & Morton 1985).
Biochemical studies of the cultured fibroblasts from our patient revealed a normal level of esterase D activity. However, molecular studies did demonstrate a dosage effect for both the plE8 and p9A7 DNA sequences. These findings, along with the cytogenetic studies, suggest a duplication 13ql4.2-13qter in this infant. Case Report
The proband, a 3.5-month-old Caucasian female, was referred for evaluation of multiple congenital anomalies. She was the product of a full-term gestation, born to
418
S C H W A R T Z ET A L
unrelated parents (both aged 24) by normal spontaneous vaginal delivery. The pregnancy was complicated by a viral illness which was treated with antibiotics. Apgar scores were 6' and 9'. Birth weight was 2740 g (3rd-10th percentile), birth length was 45 cm (3rd percentile), and head circumference was 28 cm;
