Debrus S, Berger G, de Meeus A, Sauer U, Guillaumont S, Voisin M, Bozio A, Demczuk S, Aurias A, Bouvagnet P
CRBM, CNRS-INSERM, Montpellier, France.
Hum Genet. 1996 Feb;97(2):138-44. doi: 10.1007/BF02265254.
Molecular studies have shown microdeletions in region q11 of chromosome 22 in nearly all patients with DiGeorge, velocardiofacial and conotruncal anomaly face syndromes (DGS, VCFS and CTAFS, respectively) and in a high percentage of non-syndromic familial cases of conotruncal defects (CTD). CTD account for roughly a fourth to a third of all non-syndromic congenital heart defects (CHD), thus, 22q11 could harbor a major genetic factor of CHD. We searched for a 22q11 microdeletion in familial cases of non-syndromic CTD. Thirty-six cases of various isolated CTD, that is without history of hypocalcemia, immune deficiency, absent thymus, and dysmorphic appearance, were selected. With 48F8, a cosmid probe localized in the smallest deleted region of the DiGeorge critical region (DGCR), we found no deletions by fluorescence in situ hybridization in these 36 affected individuals of 16 families with recurrent CTD. Moreover, D22S264, a microsatellite localized at the distal part of the largest deleted region, was used to genotype the patients. Thirty-two patients out of 37 were heterozygous and hence not deleted at this locus, whereas 5 were uninformative. In conclusion, there are no large deletions in familial cases of various CTD, whether these defects are identical or not within a family. This result does not rule out other minor anomalies in this chromosomal region.
分子研究表明，几乎所有患有迪乔治综合征、腭心面综合征和圆锥动脉干异常面容综合征（分别为DGS、VCFS和CTAFS）的患者以及高比例的非综合征性家族性圆锥动脉干缺损（CTD）患者的22号染色体q11区域存在微缺失。CTD约占所有非综合征性先天性心脏病（CHD）的四分之一到三分之一，因此，22q11可能含有CHD的一个主要遗传因素。我们在非综合征性CTD的家族病例中寻找22q11微缺失。选择了36例各种孤立性CTD病例，即无低钙血症、免疫缺陷、胸腺缺失和畸形外观病史的病例。使用定位在迪乔治关键区域（DGCR）最小缺失区域的黏粒探针48F8，我们在这16个有复发性CTD的家族的36名受影响个体中通过荧光原位杂交未发现缺失。此外，使用位于最大缺失区域远端的微卫星D22S264对患者进行基因分型。37名患者中有32名是杂合子，因此在该位点未缺失，而5名患者信息不明确。总之，各种CTD的家族病例中不存在大的缺失，无论这些缺陷在一个家族内是否相同。这一结果并不排除该染色体区域存在其他微小异常。
