Down syndrome chromosomal translocations

Mutational errors can extend to include more than just one base of a chromosome. Humans normally have 23 pairs of chromosomes. But mutations can produce a fetus that has an extra copy or copies of a chromosome. The unique physical appearance and retarded mental faculties associated with Down syndrome arise when three copies of chromosome 21 are present. Another type of chromosomal mutation occurs when portions of two adjacent chromosomes swap places with each other. Such a translocation mutation between chromosomes 9 and 22 lead to a certain type of leukemia. 

Chromosomal abnormalities, such as missing or extra copies, gross breaks and rejoinings (translocations) can result in disorders. Down s syndrome, or trisomy 21, is a common disorder that is a result of having three copies of chromosome 21. 

The answer is b. (Murray, pp 812—828. Scriver, pp 3—45. Sack, pp 57-84. Wilson, pp 123-148.) Cytogenetic notation provides the chromosome number (e.g., 46), the sex chromosomes, and a shorthand description of anomalies. Examples include the following 45,X indicates a female with monosomy X or Turner s syndrome 47,XX-I-2I indicates a female with trisomy 21 or Down s syndrome 46,XX,t(14 21) indicates a female with translocation Down s syndrome 45,XX—21 indicates a female with mono-... 

The answer is e. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 57-84. Wilson, pp 123-148.) Children with chromosome abnormalities often exhibit poor growth (failure to thrive) and developmental delay with an abnormal facial appearance. This baby is too young for developmental assessment, but the catlike cry should provoke suspicion of cri-du-chat syndrome. Cri-du-chat syndrome is caused by deletion of the terminal short arm of chromosome 5 [46,XX,del(5p), also abbreviated as 5p—] as depicted in panel e. When a partial deletion or duplication like this one is found, the parents must be karyotyped to determine if one carries a balanced reciprocal translocation. The other karyotypes show (a) deletion of the short arm of chromosome 4 [46,XY,del(4p) or 4p—] (b) XYY syndrome (47,XYY) (c) deletion of the long arm of chromosome 13 [46,XX,del(13q) or 13q-] (d) Klinefelter s syndrome (47,XXY). Most disorders involving excess or deficient chromosome material produce a characteristic and recognizable phenotype (e.g., Down s, cri-du-chat, or Turner s syndrome). The deletion of 4p- (panel A) produces a pattern of abnormalities (syndrome) known as Wolf-Hirschhorn syndrome deletion of 13q- produces a 13q— syndrome (no eponym). The mechanism(s) by which imbalanced chromosome material produces a distinctive phenotype is completely unknown. 

A form of Down s syndrome results from translocation between chromosomes 21 and 15 in the oocyte. In such oocytes the two chromosomes—each belonging to a different pair— form a single chromosome, and the total karyotype contains only 45 chromosomes pairs 21 and 15 are disrupted, and only one normal 21 and one normal 15 chromosome are present. When such oocytes undergo meiosis, chromosomal segregation may result in 6 different combinations in the ova a single21, a single 15, 15-15, 21 trisomy 21, 21 and 15 trisomy, a single 15-21 transloca-... 

Studies have also been carried out on individuals with defective DNA repair and with chromosome instability syndromes. The baseline SCE frequency was found to be within the normal range in individuals with ataxia-telangiectasia, Fanconi s anemia, and xeroderma pigmentosum, but a greatly increased frequency of SCE appeared in both lymphocytes and cultured bone marrow cells from individuals with Bloom s syndrome. No deviation from the normal limits has been observed in individuals with Down s syndrome or with balanced translocations or unbalanced karyotypes. 

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