Cat-eye syndrome with unusual marker chromosome probably not chromosome 22

An unusual supernumerary chromosome with a single satellite on the long arm was found in a child with manifestations of the cat-eye syndrome including apparently low-set and malformed ears, preauricular tags, micrognathia, and imperforate anus. Although G-banding suggested that this extra material was chromosome 22, this was not confirmed by several other banding techniques. After examination of the parents' chromosomes, the nature and origin of this extra chromosome remains obscure. We conclude that patients previously diagnosed as having “partial trisomy 22” with incomplete cat-eye syndrome may have a different chromosome constitution when studied by various banding techniques.     

Submicroscopic deletion in chromosome 22q11 in trizygous triplet siblings and their father Clinical variability of 22q11 deletion

A submicroscopic deletion of chromosome 22q11 was demonstrated in three triplets and in their father. Two children had the typical DiGeorge sequence with at least three of the four cardinal features: conotruncal heart disease, hypoplastic thymus and typical facial features. Hypoparathyroidism was present in one of them. The third child had features of both DiGeorge and velo-cardio-facial syndrome (VCFS). The father presented with features compatible with VCFS. This observation further illustrates the wide variability in expression of a submicroscopic deletion of 22q11, even within one family.     

利用辐射杂种板(GB4)精细定位人类新基因H-RalGDS于染色体9q34.1

目的 Ｈ－ＲａｌＧＤＳ基因是我们新近分离与克隆的人类新的Ｒａｓ相关基因,是鼠Ｒａｌ鸟嘌呤核苷酸解离刺激因子（ＲａｌＧＤＳ）在人类的同源基因。利用辐射杂种板（ｒａｄｉａｔｉｏｎ ｈｙｂｒｉｄ,ＲＨ）制图法进行该基因的精细定位。方法 根据Ｈ－ＲａｌＧＤＳ基因ｃＤＮＡ的３’不翻译区设计正反向引物,ＰＣＲ扩增人／鼠辐射体细胞杂种板（ｒａｄｉａｔｉｏｎ ｈｙｂｒｉｄ Ｇｅｎｂｒｉｄｇｅ ４ ｐａｎｅｌ）,并     

Localization of 24 cosmid clones on the human Y chromosome

Summary Twenty-four novel cosmid clones were cloned and mapped on the human Y chromosome using a panel consisting of DNA from seven individuals each having a different segment of the Y chromosome. Eight were assigned to the short arm, 15 to the long arm and 1 to the both short and long arms.     

Ordered mapping of three alpha satellite DNA subsets on human chromosome 22

We report the physical order of three alphoid DNA subsets on human chromosome 22 determined by a combination of low- and high-resolution cytological mapping. Multicolor fluorescencein situ hybridization was performed on metaphase chromosomes, interphase nuclei and extended chromatin preparations. The results visually demonstrate the presence of three distinct alphoid DNA domains at the centromeric region of chromosome 22. Two domains appear adjacent by extended chromatin hybridization, while the third one is separated by DNA that does not hybridize with any of our probes. Our data demonstrate the applicability of interphase mapping for ordering alpha satellite DNA repeat arrays. However, in our experiments, the relationship between the extremities of repeat arrays could only be studied by extended chromatin experiments.     

Isolation of human chromosome 21-specific cosmids and their uses in mapping of cosmid contigs on chromosomal subregions

Summary A cosmid library of 3×10⁵ clones has been constructed from a human x hamster hybrid cell line, 153E9a3, which contains human chromosome 21 (HC21) as the only human chromosome. From 56,500 clones of this library, 229 HC21-specific cosmids have been isolated by their hybridization to total human DNA and by their failure to hybridize to total Chinese hamster DNA. The cosmids isolated were then characterized, of these, 28 cosmids (12.2% of those tested) containedNot1 site(s), and 41 cosmids were localized on the eight subregions of HC21 by differential hybridization withAlu-PCR products obtained from a hybrid mapping panel. The cosmids localized were further integrated into the existing contigs using the end-specific probes of the clone insert. Therefore, they provided useful anchor points for contig mapping and walking.     

Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients

Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.     

Regional mapping of the gene for familial Mediterranean fever on human chromosome 16p13

Familial Mediterranean fever (FMF) is an autosomal recessively inherited inflammatory disorder characterized by recurrent short spisodes of fever, peritonitis, arthritis, and pleuritis. Recently, linkage was demonstrated between FMF and the VNTR probes 3′HVR and 5′HVR of the α-globin complex at 16p13.3 ( = 0.06?0.10, Lod_max = 9.76?14.47) and the insertion/deletion polymorphism detected by the probe CMM65 of D16S84 ( = 0.04, Lod_max = 9.17). WE have now mapped the FMF gene between the two flanking markers D16S283/D16S291 ( = 0.038) and D16S80 ( = 0.159). The proximity of the microsatellite markers in D16S283 and D16S291 to the FMF gene allows preclinical diagnosis in most pedigrees with affected individuals. © 1993 Wiley-Liss, Inc.     

Microsatellite DNA markers detects 95% of chromosome 22q11 deletions

Cono-truncal cardiac malformations account for some 50% of congenital heart defects in newborn infants. Recently, hemizygosity for chromosome 22q11.2 was reported in patients with the DiGeorge/Velo-cardio-facial syndromes (DGS/VCFS) and causally related disorders. We have explored the potential use of microsatellite DNA markers for rapid detection of 22q11 deletions in 19 newborn infants referred for cono-truncal heart malformations with associated DGS/VCFS anomalies. A failure of parental inheritance was documented in 84.2% of cases (16/19). PCR-based genotyping using microsatellite DNA markers located within the commonly deleted region allowed us either to confirm or reject a 22q11 microdeletion in 94.3% of cases (18/19) within 24 hours. This test is now currently performed in the infants referred to us for a cono-truncal heart malformation as a first intention screening for 22q11 microdeletion. Am. J. Med. Genet. 68:182–184, 1997 © 1997 Wiley-Liss, Inc.     

Thymus deficiency in an infant with a chromosome t(18;22)(q12.2;p11.2)pat rearrangement

The finding of an unbalanced t(18;22)pat chromosome rearrangement in a boy with multiple anomalies including apparent absence of the thymus is described. The observation is of interest because of the reported association of chromosome 22 rearrangements with the DiGeorge sequence. In contrast to previous reports of this association, the deletion involving chromosome 22 is confined to the short arm.     

High-Resolution genomic arrays identify CNVs that phenocopy the chromosome 22q11.2 deletion syndrome

The 22q11 Deletion Syndrome includes the overlapping phenotypes of DiGeorge/Velocardiofacial Syndromes, characterized by conotruncal heart defects, cleft palate, thymus, and parathyroid gland dysplasia. The majority (90%) of patients harbor detectable chr22q11.2 deletions, but a genetic etiology for the remainder of patients without a deletion can remain undefined despite major birth defects. We analyzed DNA from eight patients with normal 22q11 FISH studies by high-density single nucleotide polymorphism (SNP) arrays and identified potentially pathogenic copy number variants (CNVs) in four of eight patients. Two patients showed large CNVs in regions of known genomic disorders: one a deletion of distal chr22q11.2 and the other a duplication of chr5q35. A 3-Mb deletion of chr19p13.3 that includes a gene associated with conotruncal heart defects was found in a third patient. Two potentially pathogenic CNVs were found in a fourth patient: a large heterozygous deletion of chr6p24 and a smaller duplication of chr9p24. Our findings support a recent consensus statement advocating chromosomal microarray analysis as a first-line diagnostic approach for patients with multiple congenital anomalies. In patients with phenotypes suggestive of the 22q11.2 syndrome spectrum and normal FISH, microarray analysis can uncover the molecular basis of other genomic disorders whose features overlap those of 22q11.2 deletions.     

Familial transmission of a deletion of chromosome 21 derived from a translocation between chromosome 21 and an inverted chromosome 22

Chromosome analysis of a newborn boy with Down syndrome resulted in the identification of a family with an unusual derivative chromosome 22. The child has 46 chromosomes, including two chromosomes 21, one normal chromosome 22, and a derivative chromosome 22. Giemsa banding and fluorescent in situ hybridization (FISH) studies show that the derivative chromosome is chromosome 22 with evidence of both paracentric and pericentric inversions, joined to the long arm of chromosome 21 from 21q21.2 to qter. The rearrangement results in partial trisomy 21 extending from 21q21.2 to 21q terminus in the patient. The child's mother, brother, maternal aunt, and maternal grandmother are all carriers of the derivative chromosome. All have 45 chromosomes, with one normal chromosome 21, one normal chromosome 22, and the derivative chromosome 22. The rearrangement results in the absence of the short arm, the centromere, and the proximal long arm of chromosome 21 (del 21pter21q21.2) in carriers. Carriers of the derivative chromosome in this family have normal physical appearance, mild learning disabilities and poor social adjustment. Am. J. Med. Genet. 70:399–403, 1997. © 1997 Wiley-Liss, Inc.     

Full mosaic monosomy 22 in a child with DiGeorge syndrome facial appearance

We describe an abnormal premature male infant with mosaic monosomy of chromosome 22. He had a unique facial appearance, similar to those with DiGeorge syndrome, and hypertonicity, limitation of extension at major joints, and flexion contractures of all fingers. This rare chromosomal aberration has been reported previously in 6 cases, three of them being nonmosaic and three mosaic patients. There was a great variability of expression among the anomalies of these patients. However, the most common anomalies were in the face and joints. A correlation between the severity of expression and percent of monosomic cells was not clear. Am. J. Med. Genet. 76:150–153, 1998. © 1998 Wiley-Liss,Inc.     

Cognitive correlates of a functional COMT polymorphism in children with 22q11.2 deletion syndrome

Chromosome 22q11.2 deletion syndrome (22q11DS) is a common microdeletion syndrome associated with a markedly elevated risk of schizophrenia in adulthood. Cognitive impairments such as a low IQ and deficits in attention and executive function are common in childhood. The catechol O-methyltransferase (COMT) gene maps within the deleted region and is involved in the degradation of dopamine, a neurotransmitter thought to be important in cognition and the development of schizophrenia. Thus, we examined the correlation between neurocognitive deficits and a common polymorphism Val(158)Met in the COMT gene in a cohort of children with 22q11DS. Our results show that children with 22q11DS who have the Met allele have higher IQ and achievement scores and perform better on measures of prefrontal cognition, such as the Continuous Performance Task, as compared with those with the Val allele. These results confirm that the hemizygous COMT Val(158)Met genotype impacts upon cognition in children with 22q11DS.     

Saethre-Chotzen syndrome with familial translocation at chromosome 7p22

Chromosome analysis of a male infant and his mother with Saethre-Chotzen syndrome demonstrated an apparently balanced translocation, t(2;7)(p23;p22). This association lends support to localization of the gene for Saethre-Chotzen syndrome to the 7p2 region and supports further involvement of gene(s) in the 7p22 region. © 1993 Wiley-Liss, Inc.     

No evidence for an allelic association between schizophrenia and markers D22S278 and D22S283

We report a case control association study using markers D22S278 and D22S283 in 90 unrelated patients with DSMIII-R schizophrenia and 90 controls matched for ethnicity, age and sex. No differences between allele frequencies for either marker were observed when the two groups were compared (D22S278: χ² = 6.53, df = 7, P = 0.51; D22S283: χ² = 14.73, df = 15, P = 0.48). These findings fail to support previous work by others suggesting the presence of allelic association between the markers D22S278 and D22S283 and schizophrenia. Am. J. Med. Genet. 74:37–39, 1997. © 1997 Wiley-Liss, Inc.     

Submicroscopic deletions at 22q11.2: Variability of the clinical picture and delineation of a commonly deleted region

DiGeorge anomaly (DGA) and velo-cardiofacial syndrome (VCFS) are frequently associated with monosomy of chromosome region 22q11. Most patients have a submicroscopic deletion, recently estimated to be at least 1–2 Mb. It is not clear whether individuals who present with only some of the features of these conditions have the deletion, and if so, whether the size of the deletion varies from those with more classic phenotypes. We have used fluorescence in situ hybridization (FISH) to assess the deletion status of 85 individuals referred to us for molecular analysis, with a wide range of DGA-like or VCFS-like clinical features. The test probe used was the cosmid sc11.1, which detects two loci about 2 Mb apart in 22q11.2. Twenty-four patients carried the deletion. Of the deleted patients, most had classic DGA or VCFS phenotypes, but 6 deleted patients had mild phenotypes, including 2 with minor facial anomalies and velopharyngeal incompetence as the only presenting signs. Despite the great phenotypic variability among the deleted patients, none had a deletion smaller than the 2-Mb region defined by sc11.1 Smaller deletions were not detected in patients with particularly suggestive phenotypes who were not deleted for sc11.1, even when tested with two other probes from the DGA/VCFS region. © 1995 Wiley-Liss, Inc.     

Cognitive and behavior profile of preschool children with chromosome 22q11.2 deletion

A microscopic deletion of chromosome 22q11.2 has been identified in most patients with the DiGeorge, velocardiofacial syndrome, conotruncal anomaly face syndrome, and in some patients with isolated conotruncal cardiac anomalies. This study presents the neurodevelopmental outcome, including cognitive development, language development, speech, neuromuscular development, and behavioral characteristics of 40 preschool children (ages 13 to 63 months) who have been diagnosed with the 22q11.2 deletion. The impact of cardiac disease, cardiac surgery, and the palatal anomalies on this population was also studied. In the preschool years, children with a 22q11.2 deletion are most commonly found to be developmentally delayed, have mild hypotonia, and language and speech delays. The more significantly delayed children are at high risk to be subsequently diagnosed with mild or moderate mental retardation. The global delays and the variations in intelligence found are directly associated with the 22q11.2 deletion and are not explained by physical anomalies such as palatal defects or cardiac defects, or therapeutic interventions such as cardiac surgery. Our findings demonstrate that there is a pattern of significant speech disorders within this population. All of the children had late onset of verbal speech. Behavioral outcomes included both inhibition and attention disorders. Early intervention services are strongly recommended beginning in infancy to address the delays in gross motor skills, speech and language, and global developmental delays. Am. J. Med. Genet. 85:127–133, 1999. © 1999 Wiley-Liss, Inc.