Perinatal findings and molecular cytogenetic analyses of de novo interstitial deletion of 9q (9q22.3-->q31.3) associated with Gorlin syndrome.
OBJECTIVE
To present the perinatal findings and the molecular cytogenetic analyses of a de novo interstitial deletion of 9q (9q22.3-->q31.3) associated with Gorlin syndrome.


METHODS
Amniocentesis was performed at 18 weeks' gestation on a 27-year-old woman at a community hospital because of a high Down syndrome risk of 1/178, a low maternal serum alpha-fetoprotein (MSAFP) level of 0.66 multiples of the median (MoM), and a high maternal serum human chorionic gonadotrophin (MShCG) level of 3.13 MoM. The karyotype was initially determined to be 46,XY. However, fetal macrocephaly and overgrowth were found at 30 weeks' gestation. Postnatally, the infant manifested characteristic features of Gorlin syndrome. High-resolution chromosomal bandings of the peripheral blood lymphocytes, polymorphic DNA marker analysis to determine the parental origin of the deletion, array comparative genomic hybridization (CGH) to determine the extent of the chromosomal deletion, and fluorescence in situ hybridization (FISH) to determine the deletion of the PTCH gene were performed.


RESULTS
The 850-band level of resolution showed an interstitial deletion of 9q (9q22.3-->q31.3). The parental karyotypes were normal. The karyotype of the proband was 46,XY,del(9)(q22.3q31.3)de novo. Polymorphic DNA marker analysis revealed that the deletion was of paternal origin. Array CGH revealed that the deleted region was about 12 Mb, encompassing the segment from 9q22.32 to 9q31.3. FISH analysis using the BAC probe RP11-34D4 and the probe RP11-43505 indicated the deletion of the PTCH gene.


CONCLUSIONS
Fetuses with an interstitial deletion of 9q (9q22.3-->q31.3) may be associated with a low level of MSAFP and a high level of MShCG in the second trimester, and sonographic findings of overgrowth and macrocephaly in the third trimester.
Chen
Chih-Ping
CP
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan. cpc_mmh@yahoo.com
Lin
Shuan-Pei
SP
Wang
Tzu-Hao
TH
Chen
Yann-Jang
YJ
Chen
Ming
M
Wang
Wayseen
W
D000328:Adult; D000649:Amniocentesis; D001478:Basal Cell Nevus Syndrome / Q000235:genetics* / Q000473:pathology; D006063:Chorionic Gonadotropin / Q000097:blood; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008297:Male; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics; D000509:alpha-Fetoproteins / Q000032:analysis
D006063:Chorionic Gonadotropin; D005819:Genetic Markers; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D000509:alpha-Fetoproteins