Objectives To review the fetal echocardiograms of patients with total anomalous pulmonary venous connection (TAPVC) in order to

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The region commonly deleted in DiGeorge syndrome (DGS) has been localized at 22q11.1-q11.2 with the aid of a high resolution banding technique. A 22q11 specific plasmid library was constructed with a microdissection and microcloning method. Dosage analysis proved three of 144 randomly selected microclones to detect hemizygosity in two patients with DGS. Two of the clones were found to contain independent low-copy-number repetitive sequences, all of which were included in the region deleted in the DGS patients. Screening of the cosmid library and subsequent cosmid walking allowed us to obtain two cosmid contigs corresponding to the microclones within the deletion (contig 1 and contig 2), whose order fluorescence in situ hybridization identified as centromere-contig 1-contig 2-telomere on 22q. By direct selection strategy using one of the cosmids of contig 1, a 4.3 kb cDNA was obtained from fetal brain cDNA library. Sequence analysis of the cDNA revealed an open reading frame encoding 552 amino acids which had several characteristics of DNA-binding proteins. The gene, designated LZTR-1, which was transcribed in several essential fetal organs, proved to be hemizygously deleted in seven of eight DGS patients or its variants, but not in one DGS patient and GM00980. Although LZTR-1 does not locate in the shortest region of overlap, several of its structural characteristics identifying it as transcriptional regulator suggest that it plays a crucial role in embryogenesis and that haploinsufficiency of this gene may be partly related to the development of DGS.

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CHARGE syndrome is a congenital disorder caused by mutation of the chromodomain helicase DNA binding protein 7 (CHD7) gene and is characterized by multiple anomalies including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genital and/or urological abnormalities, ear anomalies, and hearing loss. In the present study, 76% of subjects had some type of endocrine disorder: short stature (72%), hypogonadotropic hypogonadism (60%), hypothyroidism (16%), and combined hypopituitarism (8%). A mutation in CHD7 was found in 80% of subjects. Here, we report the phenotypic spectrum of 25 Japanese patients with CHARGE syndrome, including their endocrinological features.