Cryptic genomic imbalances in patients with de novo or familial apparently balanced translocations and abnormal phenotype

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3137894 17 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Cryptic genomic imbalances in patients with de novo or familial
apparently balanced translocations and abnormal phenotype
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: Carriers of apparently balanced translocations are usually
phenotypically normal; however in about 6% of de novo cases, an
abnormal phenotype is present. In the current study we investigated 12
patients, six de novo and six familial, with apparently balanced
translocations and mental retardation and/or congenital malformations by
applying 1 Mb resolution array-CGH. In all de novo cases, only the
patient was a carrier of the translocation and had abnormal phenotype.
In five out of the six familial cases, the phenotype of the patient was
abnormal, although the karyotype appeared identical to other
phenotypically normal carriers of the family. In the sixth familial
case, all carriers of the translocations had an abnormal phenotype.
Results: Chromosomal and FISH analyses suggested that the rearrangements
were “truly balanced” in all patients. However, array-CGH, revealed
cryptic imbalances in three cases (3/12, 25%), two de novo (2/12,
33.3%) and one familial (1/12, 16.6%). The nature and type of
abnormalities differed among the cases. In the first case, what was
identified as a de novo t(9;15)(q31;q26.1), a complex rearrangement was
revealed involving a similar to 6.1 Mb duplication on the long arm of
chromosome 9, an similar to 10 Mb deletion and an inversion both on the
long arm of chromosome 15. These imbalances were located near the
translocation breakpoints. In the second case of a de novo
t(4;9)(q25;q21.2), an similar to 6.6 Mb deletion was identified on the
short arm of chromosome 7 which is unrelated to the translocation. In
the third case, of a familial, t(4; 7)(q13.3; p15.3), two deletions of
similar to 4.3 Mb and similar to 2.3 Mb were found, each at one of the
two translocation breakpoints. In the remaining cases the translocations
appeared balanced at 1 Mb resolution.
Conclusion: This study investigated both de novo and familial apparently
balanced translocations unlike other relatively large studies which are
mainly focused on de novo cases. This study provides additional evidence
that cryptic genomic imbalances are common in patients with abnormal
phenotype and “apparently balanced” translocations not only in de
novo but can also occur in familial cases. The use of microarrays with
higher resolution such as oligo-arrays may reveal that the frequency of
cryptic genomic imbalances among these patients is higher.
Έτος δημοσίευσης:
2008
Συγγραφείς:
Sismani, Carolina
Kitsiou-Tzeli, Sofia
Ioannides, Marios and
Christodoulou, Christodoulos
Anastasiadou, Violetta
Stylianidou,
Goula
Papadopoulou, Eleftheria
Kanavakis, Emanuel and
Kosmaidou-Aravidou, Zoe
Patsalis, Philippos C.
Περιοδικό:
Molecular Cytogenetics
Εκδότης:
BMC
Τόμος:
1
Επίσημο URL (Εκδότης):
DOI:
10.1186/1755-8166-1-15
Το ψηφιακό υλικό του τεκμηρίου δεν είναι διαθέσιμο.