PMC3590287_01
Family 1, array-CGH results.. a) Array-CGH graphical overview of 15q21.2q22.2 duplication of the proposita. b) Enlargement of the duplicated region 15q21.2q22.2 spanned 10.5 Mb from oligonucleotide A_16_P03028573(51,604,508 bp) to A_16_P20273880 (62,102,756 bp). c) Array-CGH graphical overview of 15q13.2q13.3 deletion of the mother. d) Enlargement of the deleted region spanned 2.262 Mb from oligonucleotide A_18_P12164655 (30,652,489 bp) to A_14_P200747 (32,914,140 bp).
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Furthermore, our patient, presented a duplication of 10.5Mb (chr15:51,604,508-62,102,756) on chromosome 15q21.2q22.2 (Fig. 1, A-B). Unexpectedly, array-CGH in her mother showed a deletion of 2.262 Mb (chr15:30,652,489-32,914,140) on chromosome 15q13.2q13.3 described as "recurrent 15q13.3 microdeletion syndrome". (Fig. 1, C-D).
FISH results.. a) FISH with specific subtelomeric 7q probe (red) confirmed the presence of the unbalanced translocation both in the patient and mother. b) FISH with oligonucleotide-based probe 15q13.3 (green signal) and BAC RP11-231A23 (red signal) on the metaphase of the mother in family 1 showing the deletion on a chromosome 15 (arrow). The arrowhead indicates the normal chromosome 15. c) FISH with oligonucleotide-based probe 15q13.3 (green signal) and BAC RP11-231A23 (red signal) on the metaphase of the proband in family 1 showing the duplication on a chromosome 15 (arrow). The arrowhead indicates the normal chromosome 15.FISH performed with the same probes on the metaphase of the mother showed normal signals only on both chromosome 15 (data not showed). d) FISH with oligonucleotide-based probe 22q11.21 (red signal) and BAC RP11-1143M16 (green signal) on the metaphase of the proband in family 2 confirming that large and short deletions are on the same chromosome 22. Arrowhead shows the normal chromosome 22 and arrow the deleted chromosome 22.
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FISH experiments confirmed the presence of the short deletion on the metaphases of the father and showed that the large and short deletions were both on the same chromosome 22 on the metaphases of the son (Fig. 2, C).
Pedigrees of families with inherited deletions/duplications.. (A) Pedigree of Family 1. The proposita (II, 2) carried an unbalanced 7/14 translocation and a de novo large 15q21.2q22.2 (10.5 Mb) duplication. The mother (I, 2) carried the same unbalanced 7/14 translocation and a BP4-BP5 15q13.2q13.3 deletion of 2.262 Mb (short deletion). B) Pedigree of Family 2.The propositus (II, 1) had two deletions on the same chromosome 22: a short 22q11.23 (247 Kb) deletion inherited from his father and one de novo large deletion 22q11.21 (1.417 Mb). He also showed a duplication of 484.3 Kb at 15q26.3 inherited from his father. His normal sister (II, 2) carried only the short deletion 22q11.23. Their father (I, 1) had both the short deletion of chromosome 22 and the duplication of chromosome 15.
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His mother had no abnormalities (Fig. 3, B).
PMC3590287_02
FISH results.. a) FISH with specific subtelomeric 7q probe (red) confirmed the presence of the unbalanced translocation both in the patient and mother. b) FISH with oligonucleotide-based probe 15q13.3 (green signal) and BAC RP11-231A23 (red signal) on the metaphase of the mother in family 1 showing the deletion on a chromosome 15 (arrow). The arrowhead indicates the normal chromosome 15. c) FISH with oligonucleotide-based probe 15q13.3 (green signal) and BAC RP11-231A23 (red signal) on the metaphase of the proband in family 1 showing the duplication on a chromosome 15 (arrow). The arrowhead indicates the normal chromosome 15.FISH performed with the same probes on the metaphase of the mother showed normal signals only on both chromosome 15 (data not showed). d) FISH with oligonucleotide-based probe 22q11.21 (red signal) and BAC RP11-1143M16 (green signal) on the metaphase of the proband in family 2 confirming that large and short deletions are on the same chromosome 22. Arrowhead shows the normal chromosome 22 and arrow the deleted chromosome 22.
pone.0057910.g002.jpg
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FISH experiments confirmed the presence of the short deletion on the metaphases of the father and showed that the large and short deletions were both on the same chromosome 22 on the metaphases of the son (Fig. 2, C).
Pedigrees of families with inherited deletions/duplications.. (A) Pedigree of Family 1. The proposita (II, 2) carried an unbalanced 7/14 translocation and a de novo large 15q21.2q22.2 (10.5 Mb) duplication. The mother (I, 2) carried the same unbalanced 7/14 translocation and a BP4-BP5 15q13.2q13.3 deletion of 2.262 Mb (short deletion). B) Pedigree of Family 2.The propositus (II, 1) had two deletions on the same chromosome 22: a short 22q11.23 (247 Kb) deletion inherited from his father and one de novo large deletion 22q11.21 (1.417 Mb). He also showed a duplication of 484.3 Kb at 15q26.3 inherited from his father. His normal sister (II, 2) carried only the short deletion 22q11.23. Their father (I, 1) had both the short deletion of chromosome 22 and the duplication of chromosome 15.
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His mother had no abnormalities (Fig. 3, B).
Family 2, array-CGH results.. a) Array-CGH graphical overview of 22q11.21 deletion (large deletion) of the proband. b) Enlargement of the deleted region spanned 1.417 Mb from oligonucleotide A_16_P41477688 (18,894,835 bp) to A_14_P200761(20,311,763 bp). c) Enlargement of the 22q11.23 deleted region (short deletion) spanned 247 Kb from oligonucleotide A_14_P133174 (25,664,618 bp) to A_18_P13974242 (25,911,651 bp) inherited from his father. d) Enlargement of the 15q26.3 duplicated region spanned 484.3 Kb from oligonucleotide A_16_P20368426 (100,051,182 bp) to A_14_P110953 (100,996,155 bp) of the proband and inherited from his father.
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The extent of the deletion at 22q11.21 band (large deletion) was 1.417 Mb (chr22:18,894,835-20,311,763) (Fig. 4, A-B) while the second deletion at band 22q11.23 (short deletion) (chr22:25,664,618-25,911,651) spanned 247 Kb (Fig. 4, C). Furthermore, the patient carried a duplication spanning 484.3 Kb (chr15:100,051,182-100,996,155) at q26.3 band of a chromosome 15 (Fig. 4, D).