Matsuoka R, Kimura M, Scambler P J, Morrow B E, Imamura S, Minoshima S, Shimizu N, Yamagishi H, Joh-o K, Watanabe S, Oyama K, Saji T, Ando M, Takao A, Momma K
Department of Pediatric Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Japan.
Hum Genet. 1998 Jul;103(1):70-80. doi: 10.1007/s004390050786.
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 22ql1.2 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 SD1OP1 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 role in the genesis of phenotypic variability, especially in patients with cardiovascular anomalies. No familial cases were found among CAFS patients with absent thymus/DiGeorge 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 22ql1.2. 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.
为研究圆锥动脉干颜面异常（CAF）的分子和临床特征，我们研究了183例圆锥动脉干颜面综合征（CAFS）患者的缺失大小与表型之间的相关性以及遗传方式。通过使用N25（D22S75）迪乔治关键区域（DGCR）探针进行荧光原位杂交（FISH），在180例（98%）CAFS患者中发现了22q11.2区域的半合子状态。使用9种迪乔治关键区域探针和一个SD1OP1探针（DGA II位点）进行FISH检测时，在3例（2%）CAFS患者中未发现半合子状态。这3例患者均无智力发育迟缓，仅有1例有鼻音，而在几乎所有携带缺失的180例CAFS患者中均观察到鼻音（智力发育迟缓，92%；鼻音，88%）。143个家族中有19个（13%）有家族性CAFS，16名受累父母（84%）为母亲。虽然只有2名受累父母有心血管异常，但通过FISH分析研究的16名受累父母及其受累家庭成员的缺失大小相同。这表明基因外因素可能在表型变异的发生中起作用，尤其是在有心血管异常的患者中。在无胸腺/迪乔治异常（DGA）的CAFS患者中未发现家族性病例。此外，在所有18例完全无胸腺/DGA的CAFS患者和所有6例患有精神分裂症的CAFS患者中，发现缺失在远端更长。对48例新发患者进行微卫星分析以研究缺失的起源，结果显示，65%的CAFS患者缺失起源于母亲，而64%的DGA患者缺失起源于父亲。本研究结果表明，CAF几乎总是与22q11.2缺失相关。除了该综合征的主要特征外，还发现其他值得注意的心脏外异常包括易感染、精神分裂症、脑萎缩或畸形、血小板减少、身材矮小、面神经麻痹、肛门闭锁和轻度肢体异常。
