TY - JOUR
T1 - Molecular and clinical study of 183 patients with conotruncal anomaly face syndrome
AU - Matsuoka, Rumiko
AU - Kimura, Misa
AU - Scambler, Peter J.
AU - Morrow, Bernice E.
AU - Imamura, Shin Ichiro
AU - Minoshima, Shinsei
AU - Shimizu, Nobuyoshi
AU - Yamagishi, Hiroyuki
AU - Joh-o, Kunitaka
AU - Watanabe, Seiichi
AU - Oyama, Kotaro
AU - Saji, Tsutomu
AU - Ando, Masahiko
AU - Takao, Atsuyoshi
AU - Momma, Kazuo
N1 - Funding Information:
Acknowledgements We thank Ms B. Levene for reading the manuscript. The work was supported by open research grants (1996, 1997) from the Japan Research Promotion Society for Cardiovascular Diseases, a research grant for cardiovascular diseases (5–1) from the Ministry of Health and Welfare, grants from the Japan Shipbuilding Industry Foundation (1996, 1997), and a Grant-in-Aid from the Ministry of Education, Science, and Culture of Japan. We are grateful to the patients and their family members for participating in this study. Peter J. Scambler is supported by the Birth Defects Foundation, Action Research, and the British Heart Foundation.
PY - 1998
Y1 - 1998
N2 - To investigate molecular and clinical aspects of conotruncal anomaly face (CAF), we studied the correlation between deletion size and phenotype and the mode of inheritance in 183 conotruncal anomaly face syndrome (CAFS) patients. Hemizygosity for a region of 22q11.2 was found in 180 (98%) of the patients with CAFS by fluorescence in situ hybridization (FISH) using the N25(D22S75) DiGeorge critical region (DGCR) probe. No hemizygosity was found in three (2%) of the patients with CAFS by FISH using nine DiGeorge critical region probes and a SD10P1 probe (DGA II locus). None of these three patients had mental retardation and just one had nasal intonation, which was observed in almost all of the 180 CAFS patients who carried deletions (mental retardation, 92%; nasal voice, 88%). Nineteen of 143 families (13%) had familial CAFS and 16 affected parents (84%) were mothers. Although only two of the affected parents had cardiovascular anomalies, the deletion size in the 16 affected parents and their affected family members, who were studied by FISH analysis? was the same. It indicates that extragenic factors may play a roll in the genesis of phenotypic variability, especially in patients with cardiovascular anomalies. No familial cases were found among CAFS patients with absent thymus/Di-George anomaly (DGA). Also, in all 18 CAFS patients with completely absent thymus/DGA and all 6 CAFS patients with schizophrenia, it was revealed that the deletion was longer distally. A study of the origin of the deletion using microsatellite analyses in 48 de novo patients showed that in 65% of CAFS patients it was maternal, while in 64% of DGA patients it was paternal. The findings of this study indicated that CAF was almost always associated with the deletion of 22q11.2. As well as the major features of the syndrome, other notable extracardiac anomalies were found to be: susceptibility to infection, schizophrenia, atrophy or dysmorphism of the brain, thrombocytopenia, short stature, facial palsy, anal atresia, and mild limb abnormalities.
AB - To investigate molecular and clinical aspects of conotruncal anomaly face (CAF), we studied the correlation between deletion size and phenotype and the mode of inheritance in 183 conotruncal anomaly face syndrome (CAFS) patients. Hemizygosity for a region of 22q11.2 was found in 180 (98%) of the patients with CAFS by fluorescence in situ hybridization (FISH) using the N25(D22S75) DiGeorge critical region (DGCR) probe. No hemizygosity was found in three (2%) of the patients with CAFS by FISH using nine DiGeorge critical region probes and a SD10P1 probe (DGA II locus). None of these three patients had mental retardation and just one had nasal intonation, which was observed in almost all of the 180 CAFS patients who carried deletions (mental retardation, 92%; nasal voice, 88%). Nineteen of 143 families (13%) had familial CAFS and 16 affected parents (84%) were mothers. Although only two of the affected parents had cardiovascular anomalies, the deletion size in the 16 affected parents and their affected family members, who were studied by FISH analysis? was the same. It indicates that extragenic factors may play a roll in the genesis of phenotypic variability, especially in patients with cardiovascular anomalies. No familial cases were found among CAFS patients with absent thymus/Di-George anomaly (DGA). Also, in all 18 CAFS patients with completely absent thymus/DGA and all 6 CAFS patients with schizophrenia, it was revealed that the deletion was longer distally. A study of the origin of the deletion using microsatellite analyses in 48 de novo patients showed that in 65% of CAFS patients it was maternal, while in 64% of DGA patients it was paternal. The findings of this study indicated that CAF was almost always associated with the deletion of 22q11.2. As well as the major features of the syndrome, other notable extracardiac anomalies were found to be: susceptibility to infection, schizophrenia, atrophy or dysmorphism of the brain, thrombocytopenia, short stature, facial palsy, anal atresia, and mild limb abnormalities.
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U2 - 10.1007/s004390050786
DO - 10.1007/s004390050786
M3 - Article
C2 - 9737780
AN - SCOPUS:0031659846
SN - 0340-6717
VL - 103
SP - 70
EP - 80
JO - Human Genetics
JF - Human Genetics
IS - 1
ER -