DETECTION OF BREAKPOINTS IN SUBMICROSCOPIC CHROMOSOMAL TRANSLOCATION, ILLUSTRATING AN IMPORTANT MECHANISM FOR GENETIC DISEASE

J. Lamb; P. C. Harris; R. H. Lindenbaum; S. T. Reeders; A. O.M. Wilkie; V. J. Buckle; N. J. Barton; D. J. Weatherall; D. R. Higgs

doi:10.1016/S0140-6736(89)92995-4

DETECTION OF BREAKPOINTS IN SUBMICROSCOPIC CHROMOSOMAL TRANSLOCATION, ILLUSTRATING AN IMPORTANT MECHANISM FOR GENETIC DISEASE

J. Lamb, P. C. Harris, R. H. Lindenbaum, S. T. Reeders, A. O.M. Wilkie, V. J. Buckle, N. J. Barton, D. J. Weatherall, D. R. Higgs

Nephrology and Hypertension

Research output: Contribution to journal › Article › peer-review

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Abstract

A 3-year-old boy presented with α-thalassaemia, dysmorphic features, and mental handicap. His younger sister is also mentally retarded, but haematologically normal. High resolution cytogenetic analysis revealed a normal karyotype in all family members. However, a combination of DNA analysis and in situ hybridisation demonstrated that the mother has a previously unsuspected balanced reciprocal translocation between the tips of the short arms of chromosomes 1 and 16, and that the α-globin gene complex (which maps to the tip of chromosome 16) is included in the translocated segment. Both of her children have inherited one of the translocation chromosomes in an unbalanced fashion: the boy has the derived chromosome 16, and therefore has α-thalassaemia, whilst the girl has the derived chromosome 1. Such cytogenetically invisible subtelomeric translocations are probably an important and hitherto unrecognised cause of genetic disease.

Original language	English (US)
Pages (from-to)	819-824
Number of pages	6
Journal	The Lancet
Volume	334
Issue number	8667
DOIs	https://doi.org/10.1016/S0140-6736(89)92995-4
State	Published - Oct 7 1989

ASJC Scopus subject areas

Medicine(all)

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10.1016/S0140-6736(89)92995-4

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@article{ae2eb595dffd4ded8785069466979119,

title = "DETECTION OF BREAKPOINTS IN SUBMICROSCOPIC CHROMOSOMAL TRANSLOCATION, ILLUSTRATING AN IMPORTANT MECHANISM FOR GENETIC DISEASE",

abstract = "A 3-year-old boy presented with α-thalassaemia, dysmorphic features, and mental handicap. His younger sister is also mentally retarded, but haematologically normal. High resolution cytogenetic analysis revealed a normal karyotype in all family members. However, a combination of DNA analysis and in situ hybridisation demonstrated that the mother has a previously unsuspected balanced reciprocal translocation between the tips of the short arms of chromosomes 1 and 16, and that the α-globin gene complex (which maps to the tip of chromosome 16) is included in the translocated segment. Both of her children have inherited one of the translocation chromosomes in an unbalanced fashion: the boy has the derived chromosome 16, and therefore has α-thalassaemia, whilst the girl has the derived chromosome 1. Such cytogenetically invisible subtelomeric translocations are probably an important and hitherto unrecognised cause of genetic disease.",

author = "J. Lamb and Harris, {P. C.} and Lindenbaum, {R. H.} and Reeders, {S. T.} and Wilkie, {A. O.M.} and Buckle, {V. J.} and Barton, {N. J.} and Weatherall, {D. J.} and Higgs, {D. R.}",

note = "Funding Information: We thank Prof E. R. Huehns for bringing this family to our attention; Dr G. Katz and Dr D. Challis for providing clinical details; H. Ayyub for technical assistance; Dr R. D. Nicholls for helpful discussions; Prof M. Litt for allowing us to use probe 1-79 and Prof A. Jeffreys for XMS1 and &lgr;MS32; and Dr J. B. Clegg and Dr W. G. Wood for helpful comments. A. O. M. W. was supported by an MRC training fellowship, and this work was supported in part by a grant from Action Research for the Crippled Child (National Fund for Research into Crippling Diseases).",

year = "1989",

month = oct,

day = "7",

doi = "10.1016/S0140-6736(89)92995-4",

language = "English (US)",

volume = "334",

pages = "819--824",

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T1 - DETECTION OF BREAKPOINTS IN SUBMICROSCOPIC CHROMOSOMAL TRANSLOCATION, ILLUSTRATING AN IMPORTANT MECHANISM FOR GENETIC DISEASE

AU - Lamb, J.

AU - Harris, P. C.

AU - Lindenbaum, R. H.

AU - Reeders, S. T.

AU - Wilkie, A. O.M.

AU - Buckle, V. J.

AU - Barton, N. J.

AU - Weatherall, D. J.

AU - Higgs, D. R.

N1 - Funding Information: We thank Prof E. R. Huehns for bringing this family to our attention; Dr G. Katz and Dr D. Challis for providing clinical details; H. Ayyub for technical assistance; Dr R. D. Nicholls for helpful discussions; Prof M. Litt for allowing us to use probe 1-79 and Prof A. Jeffreys for XMS1 and &lgr;MS32; and Dr J. B. Clegg and Dr W. G. Wood for helpful comments. A. O. M. W. was supported by an MRC training fellowship, and this work was supported in part by a grant from Action Research for the Crippled Child (National Fund for Research into Crippling Diseases).

PY - 1989/10/7

Y1 - 1989/10/7

N2 - A 3-year-old boy presented with α-thalassaemia, dysmorphic features, and mental handicap. His younger sister is also mentally retarded, but haematologically normal. High resolution cytogenetic analysis revealed a normal karyotype in all family members. However, a combination of DNA analysis and in situ hybridisation demonstrated that the mother has a previously unsuspected balanced reciprocal translocation between the tips of the short arms of chromosomes 1 and 16, and that the α-globin gene complex (which maps to the tip of chromosome 16) is included in the translocated segment. Both of her children have inherited one of the translocation chromosomes in an unbalanced fashion: the boy has the derived chromosome 16, and therefore has α-thalassaemia, whilst the girl has the derived chromosome 1. Such cytogenetically invisible subtelomeric translocations are probably an important and hitherto unrecognised cause of genetic disease.

AB - A 3-year-old boy presented with α-thalassaemia, dysmorphic features, and mental handicap. His younger sister is also mentally retarded, but haematologically normal. High resolution cytogenetic analysis revealed a normal karyotype in all family members. However, a combination of DNA analysis and in situ hybridisation demonstrated that the mother has a previously unsuspected balanced reciprocal translocation between the tips of the short arms of chromosomes 1 and 16, and that the α-globin gene complex (which maps to the tip of chromosome 16) is included in the translocated segment. Both of her children have inherited one of the translocation chromosomes in an unbalanced fashion: the boy has the derived chromosome 16, and therefore has α-thalassaemia, whilst the girl has the derived chromosome 1. Such cytogenetically invisible subtelomeric translocations are probably an important and hitherto unrecognised cause of genetic disease.

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DETECTION OF BREAKPOINTS IN SUBMICROSCOPIC CHROMOSOMAL TRANSLOCATION, ILLUSTRATING AN IMPORTANT MECHANISM FOR GENETIC DISEASE

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