Abstract
A male child with multiple congenital anomalies initially was clinically diagnosed as having Smith-Lemli-Opitz syndrome (SLOS). Subsequent cytogenetic studies revealed an interstitial deletion of 17p11.2, which is associated with Smith-Magenis syndrome (SMS). Biochemical studies were not supportive of a diagnosis of SLOS, and the child did not display the typical SMS phenotype. The father's karyotype showed a paracentric inversion of 17p, with breakpoints in p11.2 and p13.3, and the same inversion was also found in two of the father's sisters. FISH analyses of the deleted and inverted 17p chromosomes indicated that the deletion was similar to that typically seen in SMS patients and was found to bracket the proximal inversion breakpoint. Available family members were genotyped at 33 polymorphic DNA loci in 17p. These studies determined that the deletion was of paternal origin and that the inversion was of grandpaternal origin. Haplotype analysis demonstrated that the 17p11.2 deletion arose following a recombination event involving the father's normal and inverted chromosome 17 homologues. A mechanism is proposed to explain the simultaneous deletion and apparent 'reinversion' of the recombinant paternal chromosome. These findings have implications for prenatal counseling of carriers of paracentric inversions, who typically are considered to bear minimal reproductive risk.
| Original language | English |
|---|---|
| Pages (from-to) | 1184-1193 |
| Number of pages | 10 |
| Journal | American Journal of Human Genetics |
| Volume | 60 |
| Issue number | 5 |
| Publication status | Published - 1997 |
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ASJC Scopus subject areas
- Genetics
Cite this
Molecular analysis of deletion (17)(p11.2p11.2) in a Family segregating a 17p paracentric inversion : Implications for carriers of paracentric inversions. / Yang, Samuel P.; Bidichandani, Sanjay I.; Figuera, Luis E.; Juyal, Ramesh C.; Saxon, Paul J.; Baldini, Antonio; Patel, Pragna I.
In: American Journal of Human Genetics, Vol. 60, No. 5, 1997, p. 1184-1193.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular analysis of deletion (17)(p11.2p11.2) in a Family segregating a 17p paracentric inversion
T2 - Implications for carriers of paracentric inversions
AU - Yang, Samuel P.
AU - Bidichandani, Sanjay I.
AU - Figuera, Luis E.
AU - Juyal, Ramesh C.
AU - Saxon, Paul J.
AU - Baldini, Antonio
AU - Patel, Pragna I.
PY - 1997
Y1 - 1997
N2 - A male child with multiple congenital anomalies initially was clinically diagnosed as having Smith-Lemli-Opitz syndrome (SLOS). Subsequent cytogenetic studies revealed an interstitial deletion of 17p11.2, which is associated with Smith-Magenis syndrome (SMS). Biochemical studies were not supportive of a diagnosis of SLOS, and the child did not display the typical SMS phenotype. The father's karyotype showed a paracentric inversion of 17p, with breakpoints in p11.2 and p13.3, and the same inversion was also found in two of the father's sisters. FISH analyses of the deleted and inverted 17p chromosomes indicated that the deletion was similar to that typically seen in SMS patients and was found to bracket the proximal inversion breakpoint. Available family members were genotyped at 33 polymorphic DNA loci in 17p. These studies determined that the deletion was of paternal origin and that the inversion was of grandpaternal origin. Haplotype analysis demonstrated that the 17p11.2 deletion arose following a recombination event involving the father's normal and inverted chromosome 17 homologues. A mechanism is proposed to explain the simultaneous deletion and apparent 'reinversion' of the recombinant paternal chromosome. These findings have implications for prenatal counseling of carriers of paracentric inversions, who typically are considered to bear minimal reproductive risk.
AB - A male child with multiple congenital anomalies initially was clinically diagnosed as having Smith-Lemli-Opitz syndrome (SLOS). Subsequent cytogenetic studies revealed an interstitial deletion of 17p11.2, which is associated with Smith-Magenis syndrome (SMS). Biochemical studies were not supportive of a diagnosis of SLOS, and the child did not display the typical SMS phenotype. The father's karyotype showed a paracentric inversion of 17p, with breakpoints in p11.2 and p13.3, and the same inversion was also found in two of the father's sisters. FISH analyses of the deleted and inverted 17p chromosomes indicated that the deletion was similar to that typically seen in SMS patients and was found to bracket the proximal inversion breakpoint. Available family members were genotyped at 33 polymorphic DNA loci in 17p. These studies determined that the deletion was of paternal origin and that the inversion was of grandpaternal origin. Haplotype analysis demonstrated that the 17p11.2 deletion arose following a recombination event involving the father's normal and inverted chromosome 17 homologues. A mechanism is proposed to explain the simultaneous deletion and apparent 'reinversion' of the recombinant paternal chromosome. These findings have implications for prenatal counseling of carriers of paracentric inversions, who typically are considered to bear minimal reproductive risk.
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UR - http://www.scopus.com/inward/citedby.url?scp=0030982921&partnerID=8YFLogxK
M3 - Article
C2 - 9150166
AN - SCOPUS:0030982921
VL - 60
SP - 1184
EP - 1193
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 5
ER -