Abstract
The basic genomic defect in Wolf-Hirschhorn syndrome (WHS), including isolated 4p deletions and various unbalanced de novo 4p;autosomal translocations and above all t(4p;8p), is heterogeneous. Olfactory receptor gene clusters (ORs) on 4p were demonstrated to mediate a group of WHS-associated t(4p;8p)dn translocations. The breakpoint of a 4-Mb isolated deletion was also recently reported to fall within the most distal OR. However, it is still unknown whether ORs mediate all 4p-autosomal translocations, or whether they are involved in the origin of isolated 4p deletions. Another unanswered question is whether a parental inversion polymorphism on 4p16 can act as predisposing factor in the origin of WHS-associated rearrangements. We investigated the involvement of the ORs in the origin of 73 WHS-associated rearrangements. No hotspots for rearrangements were detected. Breakpoints on 4p occurred within the proximal or the distal olfactory receptor gene cluster in 8 of 73 rearrangements (11%). These were five t(4p;8p) translocations, one t(4p;7p) translocation and two isolated terminal deletions. ORs were not involved in one additional t(4p;8p) translocation, in a total of nine different 4p;autosomal translocations and in the majority of isolated deletions. The presence of a parental inversion polymorphism on 4p was investigated in 30 families in which the 4p rearrangements, all de novo, were tested for parental origin (7 were maternal and 23 paternal). It was detected only in the mothers of 3 t(4p;8p) cases. We conclude that WHS-associated chromosome changes are not usually mediated by low copy repeats. The 4p16.3 inversion polymorphism is not a risk factor for their origin.
| Original language | English |
|---|---|
| Pages (from-to) | 423-430 |
| Number of pages | 8 |
| Journal | Human Genetics |
| Volume | 122 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Dec 2007 |
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ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Wolf-Hirschhorn syndrome-associated chromosome changes are not mediated by olfactory receptor gene clusters nor by inversion polymorphism on 4p16. / Zollino, Marcella; Lecce, Rosetta; Murdolo, Marina; Orteschi, Daniela; Marangi, Giuseppe; Selicorni, Angelo; Midro, Alina; Sorge, Giovanni; Zampino, Giuseppe; Memo, Luigi; Battaglia, Domenica; Petersen, Michael; Pandelia, Effie; Gyftodimou, Yolanda; Faravelli, Francesca; Tenconi, Romano; Garavelli, Livia; Mazzanti, Laura; Fischetto, Rita; Cavalli, Pietro; Savasta, Salvatore; Rodriguez, Laura; Neri, Giovanni.
In: Human Genetics, Vol. 122, No. 5, 12.2007, p. 423-430.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Wolf-Hirschhorn syndrome-associated chromosome changes are not mediated by olfactory receptor gene clusters nor by inversion polymorphism on 4p16
AU - Zollino, Marcella
AU - Lecce, Rosetta
AU - Murdolo, Marina
AU - Orteschi, Daniela
AU - Marangi, Giuseppe
AU - Selicorni, Angelo
AU - Midro, Alina
AU - Sorge, Giovanni
AU - Zampino, Giuseppe
AU - Memo, Luigi
AU - Battaglia, Domenica
AU - Petersen, Michael
AU - Pandelia, Effie
AU - Gyftodimou, Yolanda
AU - Faravelli, Francesca
AU - Tenconi, Romano
AU - Garavelli, Livia
AU - Mazzanti, Laura
AU - Fischetto, Rita
AU - Cavalli, Pietro
AU - Savasta, Salvatore
AU - Rodriguez, Laura
AU - Neri, Giovanni
PY - 2007/12
Y1 - 2007/12
N2 - The basic genomic defect in Wolf-Hirschhorn syndrome (WHS), including isolated 4p deletions and various unbalanced de novo 4p;autosomal translocations and above all t(4p;8p), is heterogeneous. Olfactory receptor gene clusters (ORs) on 4p were demonstrated to mediate a group of WHS-associated t(4p;8p)dn translocations. The breakpoint of a 4-Mb isolated deletion was also recently reported to fall within the most distal OR. However, it is still unknown whether ORs mediate all 4p-autosomal translocations, or whether they are involved in the origin of isolated 4p deletions. Another unanswered question is whether a parental inversion polymorphism on 4p16 can act as predisposing factor in the origin of WHS-associated rearrangements. We investigated the involvement of the ORs in the origin of 73 WHS-associated rearrangements. No hotspots for rearrangements were detected. Breakpoints on 4p occurred within the proximal or the distal olfactory receptor gene cluster in 8 of 73 rearrangements (11%). These were five t(4p;8p) translocations, one t(4p;7p) translocation and two isolated terminal deletions. ORs were not involved in one additional t(4p;8p) translocation, in a total of nine different 4p;autosomal translocations and in the majority of isolated deletions. The presence of a parental inversion polymorphism on 4p was investigated in 30 families in which the 4p rearrangements, all de novo, were tested for parental origin (7 were maternal and 23 paternal). It was detected only in the mothers of 3 t(4p;8p) cases. We conclude that WHS-associated chromosome changes are not usually mediated by low copy repeats. The 4p16.3 inversion polymorphism is not a risk factor for their origin.
AB - The basic genomic defect in Wolf-Hirschhorn syndrome (WHS), including isolated 4p deletions and various unbalanced de novo 4p;autosomal translocations and above all t(4p;8p), is heterogeneous. Olfactory receptor gene clusters (ORs) on 4p were demonstrated to mediate a group of WHS-associated t(4p;8p)dn translocations. The breakpoint of a 4-Mb isolated deletion was also recently reported to fall within the most distal OR. However, it is still unknown whether ORs mediate all 4p-autosomal translocations, or whether they are involved in the origin of isolated 4p deletions. Another unanswered question is whether a parental inversion polymorphism on 4p16 can act as predisposing factor in the origin of WHS-associated rearrangements. We investigated the involvement of the ORs in the origin of 73 WHS-associated rearrangements. No hotspots for rearrangements were detected. Breakpoints on 4p occurred within the proximal or the distal olfactory receptor gene cluster in 8 of 73 rearrangements (11%). These were five t(4p;8p) translocations, one t(4p;7p) translocation and two isolated terminal deletions. ORs were not involved in one additional t(4p;8p) translocation, in a total of nine different 4p;autosomal translocations and in the majority of isolated deletions. The presence of a parental inversion polymorphism on 4p was investigated in 30 families in which the 4p rearrangements, all de novo, were tested for parental origin (7 were maternal and 23 paternal). It was detected only in the mothers of 3 t(4p;8p) cases. We conclude that WHS-associated chromosome changes are not usually mediated by low copy repeats. The 4p16.3 inversion polymorphism is not a risk factor for their origin.
UR - http://www.scopus.com/inward/record.url?scp=36348932115&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36348932115&partnerID=8YFLogxK
U2 - 10.1007/s00439-007-0412-5
DO - 10.1007/s00439-007-0412-5
M3 - Article
C2 - 17676343
AN - SCOPUS:36348932115
VL - 122
SP - 423
EP - 430
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 5
ER -