Clinical Photos - Chromosome structure abnormality

© 2009 NHS National Genetics Education and Development Centre Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

Conditions caused by abnormalities in chromosome structure

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Fig. 2.1 ©Scion Publishing Ltd

Child with 22q11 deletion. Note small mouth, narrow nose and upward slant of her eyes.



G-banded karyotypes of chromosomesThere is a balanced translocation. Chromosomes 1 and 22 have exchanged segments (arrows). The translocation is described as 46,XX,t(1:22)(q25;q13)



How the 1;22 translocation originatedChromosome 1 and 22 broke at the positions indicated by the arrows, and the cell’s DNA repair machinery rejoined the ends to form the two derivative chromosomes as shown. The derivative chromosomes are labelled der(1) and der(22).





G-banded karyotypeShe has inherited a normal chromosome 1 but her translocated chromosome 22 (arrow). She is trisomic for the portion of chromosome 1 distal to 1q25, the translocation breakpoint, and monosomic for chromosome 22 distal to 22q13.



A Robertsonian translocationThe inset shows how this common type of chromosome abnormality arises. The short arms of all the acrocentric chromosomes (13, 14, 15, 21, 22) contain similar DNA. Inappropriate recombination between two non-homologous chromosomes produces the fusion chromosome, which functions as a normal single chromosome in mitosis. The small acentric fragment comprising the two distal short arms is lost.



During meiosis I matching chromosome segments pair. If one chromosome has an inversion compared to its homolog, they usually form a looped structure.


Fig. Disease box 3 ©Scion Publishing Ltd

(a-c) Reproduced with permission from Dr Ursula Bellugi, The Salk Institute for Biological Studies.

(a) “Williams-Beuren syndrome” (b) “Drawings by people with Williams-Beuren syndrome”


Fig. 4.3 ©Scion Publishing LtdPhotos courtesy of Dr Bert de Vries

A child with multiple congenital abnormalities suggestive of a chromosome abnormality

She has severe mental retardation, growth retardation, microcephaly and dysmorphism of the face and hands (epicanthic folds, hypertelorism, arched eyebrows, low-set ears, short philtrum, open mouth appearance, full lips, irregular position of the lower teeth, clinodactyly of the 5th finger and distal brachydactyly).



Example of array-CGH output



22q11 metaphase FISH

The green spots are a control probe, used to identify the two copies of chromosome 22 and confirm that hybridization has taken place. The red spots are the TUPLE1 probe. Only one of the two copies of chromosome 22 contains the sequence that hybridizes to this probe.



The 15q11q13 deletion in Prader-Willi or Angelman syndrome patients is sometimes just visible under the microscope in a standard cytogenetic preparation. In most cases a molecular test (FISH or PCR) is needed to make the diagnosis.


Fig. 8.2 ©Scion Publishing Ltd Photo. courtesy of Dr John Yin

Typical appearance of acute lymphocytic leukaemia. Small blasts with high nuclear – cytoplasmic ratio, some with prominent nucleoli.


Fig. 12.5 ©Scion Publishing Ltd Reproduced from Molecular Cancer, 2: 30; © 2003 Duensing et al.; licensee BioMed Central Ltd

Burkitt’s lymphoma(a) Histology, and (b) a karyotype showing the characteristic 8;14 translocation. Additional chromosome abnormalities are also present, as is usually the case in neoplasia.


Fig. 12.10 ©Scion Publishing LtdPhoto. courtesy of Dr Christine Harrison

Metaphase with TEL-AML1 fusionThe green signal is on the normal chromosome 12, one red signal is in the normal chromosome 21 and one is on the derived chromosome 12. The yellow TEL-AML1 fusion signal is on the derived chromosome 21.


45,XX,der(14;21)(q10;q10)


46,XX,t(4;15)(q2?1.3;q13)


46,XX,t(9;22)(q34;q11)


ish der(9)(ABL-),der(22)(BCRsp+conABLsp+,ABLsp+,BCRsp+)


46,X,r(X)


ins(22;9)(q11;q13q34)


46,XY.ish del(15)(q11.2q11.2)(SNRPN-)


46,XY.ish del(15)(q11.2q11.2)(SNRPN-)


46,XX.ish del(22)(q11.2q11.2)(TUPLE1-)


46,XX.ish del(22)(q11.2q11.2)(TUPLE1-)


46,X,del(X)(p21.1)


46,XX,del(4)(p15.2p16.?2)


ish del(7)(q11.23q11.23)(ELN-)

Williams syndrome

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Clinical Photos - Chromosome structure abnormality