McQuade L, Christodoulou J, Budarf M, Sachdev R, Wilson M, Emanuel B, Colley A
VCFS Research Group, Clinical Sciences, Royal Alexandra Hospital for Children, Parramatta, New South Wales, Australia.
Am J Med Genet. 1999 Sep 3;86(1):27-33.
The apparent lack of genotype/phenotype correlation in patients with the DiGeorge anomaly and velocardiofacial syndrome (DGA/VCFS; the "22q11 deletion syndrome") indicates a complex genetic condition. Most cases, whatever the phenotype, have a 1.5-3 Mb chromosomal deletion that includes the minimal DiGeorge critical region (MDGCR). Another potential critical region on 22q11 has been suggested based on two patients with distal deletions outside the MDGCR. We report on a patient with a VCFS phenotype who has a deletion, mapped by short tandem repeat polymorphic loci and fluorescence in situ hybridization analysis, distal to and not overlapping the MDGCR. This patient is deleted for several genes, including the T-box 1 gene (TBX1; a transcription regulator expressed early in embryogenesis) and catechol-O-methyltransferase (COMT; involved in neurotransmitter metabolism). We discuss the role these two genes may play in the clinical phenotype of the patient.
患有DiGeorge异常和心脏颜面综合征(DGA/VCFS;“22q11缺失综合征”)的患者中明显缺乏基因型/表型相关性,这表明这是一种复杂的遗传疾病。大多数病例,无论其表型如何,都有一个1.5 - 3 Mb的染色体缺失,其中包括最小DiGeorge关键区域(MDGCR)。基于两名在MDGCR之外有远端缺失的患者,有人提出了22q11上的另一个潜在关键区域。我们报告了一名患有VCFS表型的患者,通过短串联重复多态性位点和荧光原位杂交分析确定其缺失位于MDGCR远端且与之不重叠。该患者缺失了几个基因,包括T盒1基因(TBX1;一种在胚胎发育早期表达的转录调节因子)和儿茶酚-O-甲基转移酶(COMT;参与神经递质代谢)。我们讨论了这两个基因可能在该患者临床表型中所起的作用。