American Journal of Medical Genetics 40:201-205 (1991)
Familial Holoprosencephaly Associated With a Translocation Breakpoint at Chromosomal Position 7q36 Androniki G. Hatziioannou, Celeste M. Krauss, Michael B. Lewis, and Thanos D. Halazonetis Department of Pediatric Dentistry, Tufts University School of Dental Medicine (A.G.H.), Department of Obstetrics and Gynecology, Brigham and Women’s Hospital (C.MX.), Department of Plastic Surgery, New England Medical Center (M.B.L.), Departments of Medical Genetics, Harvard Community Health Plan (C.M.K.), and Genetics (T.D.H.), Harvard Medical School, Boston, Massachusetts A familial balanced t(7;9) (q36;q34) was reported recently. Analysis of the craniofacial features of 3 of the sibs showed signs of holoprosencephaly. Two of the sibs have an unbalanced derivative chromosome leading to del(7) (q36) and dup(9) (q34), while the other has a cytogenetically balanced translocation. These findings, together with several reports associating holoprosencephalywith terminal 7q deletions, indicate that a putative locus for holoprosencephaly resides at or near 7q36. It should now be feasible to clone this locus.
KEY WORDS: holoprosencephaly, median cleft lip, balanced translocation, dup(9) (q3), de1(7)(q3) INTRODUCTION A previous report described a family with a maternal (7;9)(q36;q34)translocation [Krauss et al., 19891. Two offspring, a brother (patient 11-2) and a sister (patient 11-81, have inherited this cytogenetically balanced translocation, while in 2 other sisters (patients 11-1and 11-5),an unbalanced segregation has lead to de1(7)(q36) and dup(9)(q34).In this study we examined the craniofacia1 development as sibs 11-1,11-2, and 11-5. CLINICAL REPORTS The patients presented here have been described previously [Krauss et al., 19891. In this report we emphasize findings that relate to their craniofacial development and lead to the diagnosis of holoprosencephaly.
Received for publication July 19,1990;revision received November 1, 1990. Thanos D. Halazonetis, D.D.S., Ph.D., is now at Merck, Sharp and Dohme Research Laboratories, WP16-3,West Point, PA 19486. Address reprint requests there.
0 1991 Wiley-Liss, Inc.
Patient 11-1 At the time of examination patient 11-1was a 19-yearold female of Greek origin with de1(7)(q36)and dup(9) (q34) due to an unbalanced segregation of a maternal (7;9)(q36;q34)translocation. At delivery her weight was 2.75 kg (15th centile), and she had microcephaly and hypotelorism. Her psychomotor development was delayed. She started walking at the 4th year of life and has had moderate to severe mental retardation. At the time of this examination her height was 141 cm (50th centile for a 10-year-old)and the head circumference (OFC) 48 cm (
Familial Holoprosencephaly Associated With a Translocation Breakpoint at Chromosomal Position 7q36 Androniki G. Hatziioannou, Celeste M. Krauss, Michael B. Lewis, and Thanos D. Halazonetis Department of Pediatric Dentistry, Tufts University School of Dental Medicine (A.G.H.), Department of Obstetrics and Gynecology, Brigham and Women’s Hospital (C.MX.), Department of Plastic Surgery, New England Medical Center (M.B.L.), Departments of Medical Genetics, Harvard Community Health Plan (C.M.K.), and Genetics (T.D.H.), Harvard Medical School, Boston, Massachusetts A familial balanced t(7;9) (q36;q34) was reported recently. Analysis of the craniofacial features of 3 of the sibs showed signs of holoprosencephaly. Two of the sibs have an unbalanced derivative chromosome leading to del(7) (q36) and dup(9) (q34), while the other has a cytogenetically balanced translocation. These findings, together with several reports associating holoprosencephalywith terminal 7q deletions, indicate that a putative locus for holoprosencephaly resides at or near 7q36. It should now be feasible to clone this locus.
KEY WORDS: holoprosencephaly, median cleft lip, balanced translocation, dup(9) (q3), de1(7)(q3) INTRODUCTION A previous report described a family with a maternal (7;9)(q36;q34)translocation [Krauss et al., 19891. Two offspring, a brother (patient 11-2) and a sister (patient 11-81, have inherited this cytogenetically balanced translocation, while in 2 other sisters (patients 11-1and 11-5),an unbalanced segregation has lead to de1(7)(q36) and dup(9)(q34).In this study we examined the craniofacia1 development as sibs 11-1,11-2, and 11-5. CLINICAL REPORTS The patients presented here have been described previously [Krauss et al., 19891. In this report we emphasize findings that relate to their craniofacial development and lead to the diagnosis of holoprosencephaly.
Received for publication July 19,1990;revision received November 1, 1990. Thanos D. Halazonetis, D.D.S., Ph.D., is now at Merck, Sharp and Dohme Research Laboratories, WP16-3,West Point, PA 19486. Address reprint requests there.
0 1991 Wiley-Liss, Inc.
Patient 11-1 At the time of examination patient 11-1was a 19-yearold female of Greek origin with de1(7)(q36)and dup(9) (q34) due to an unbalanced segregation of a maternal (7;9)(q36;q34)translocation. At delivery her weight was 2.75 kg (15th centile), and she had microcephaly and hypotelorism. Her psychomotor development was delayed. She started walking at the 4th year of life and has had moderate to severe mental retardation. At the time of this examination her height was 141 cm (50th centile for a 10-year-old)and the head circumference (OFC) 48 cm (
