Chromosome 22q11 deletions in patients with conotruncal heart defects.

We performed this study to determine the frequency of 22q11 deletions and associated phenotypic features and abnormalities in conotruncal heart defects. Sixty-one patients with conotruncal heart defects, including tetralogy of Fallot (TOF; n = 32), pulmonary atresia/ventricular septal defect (PAVSD; n = 12), double-outlet right ventricle (DORV; n = 5), transposition of the great arteries (TGA; n = 4 ), truncus arteriosus (TA; n = 4), subpulmonary ventricular septal defect (SPVSD; n = 3), and interrupted aortic arch (IAA; n = 1), were enrolled in this study and screened for 22q11 deletions by the fluorescence in situ hybridization technique. Phenotypic features and associated abnormalities, including submucosal cleft palate, abnormal facies, square nose, nasal voice, abnormal ears, long and slender fingers, delayed development, mental retardation, delayed growth, short stature, and hypocalcemia, were examined in these patients. Nine of 61 patients (14.8%) had 22q11 deletions, including 100% of IAA, 50% of TA, 33.3% of SPVSD, 33.3% of PAVSD, and 3.1% of TOF. Deletions were not detected in DORV and TGA. In all patients with 22q11 deletions, > or =1 phenotypic features or associated abnormalities were observed. A subgroup of patients with IAA, TA, SPVSD, and PAVSD associated with phenotypic features or abnormalities warrants evaluation for the presence of 22q11 deletions.

Fluorescence in situ hybridization: a rapid analysis to verify chromosome aberrations.

We applied fluorescence in situ hybridization (FISH) to assess the presence of structural rearrangement and numerical chromosome aberrations in both metaphase chromosome and interphase nuclei. For this purpose, the biotinylated repetitive alpha-satellite DNA probes for chromosome 1, 18 and 8 (pUC1.77, L1.84 and pJM128) were used to identify tetraploid mosaicism, ring chromosome 18 and trisomy 8 mosaicism for pre-, post-natal and tumor diagnosis respectively. Utilizing this approach, we showed the usefulness of FISH for routine clinical cytogenetics in addition to chromosome banding techniques. The chromosome aberrations with unknown or unclear origin, detected by chromosome analysis, could be confirmed accurately and rapidly.

Williams syndrome and the elastin gene in Thai patients.

Williams syndrome (WS) has long been known as a complex disorder of dysmorphic facial features, described as elfin face, mental retardation or learning disability, loquacious personality, and supravalvular aortic stenosis. The etiology is now known to be due to deletion of the elastin gene (ELN) on long arm of chromosome 7. Thai patients were previously reported by clinical diagnosis. This study reports the first two cases of WS with ELN deletion diagnosed by fluorescent in situ hybridization (FISH) technique. Clinically, hyperacusis is a common finding in WS associated with otitis media. Neither of the patients had hyperacusis, but one of them had bilateral sensorineural hearing loss, which to our knowledge, has never been reported.

Chromosome 22q11 deletion syndrome: the first three cases reported in Thailand.

The DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes were originally described as separate disorders due to different concerns regarding phenotypes. However, all these disorders have some common clinical manifestations, including congenital heart defect, facial anomaly, and developmental delay. It is now clear that most cases of these syndromes have a common cause resulting from microdeletion of chromosome 22q11. This study reports the first three cases of Thai children presented with developmental delays. All are females who were known cases of congenital heart diseases. Their minor facial anomalies were subtle and not previously recognized as of any syndromes. The chromosome study by fluorescent in situ hybridization technique yielded microdeletion of chromosome 22q11. Without known prevalence in Asian populations, except in Japanese children, further study for chromosome 22q11 deletion syndrome in Asian children with conotruncal heart defects, who also have minor facial anomalies or developmental delays, should be undertaken.

Multicolor fluorescence in situ hybridization on metaphase chromosomes and interphase Halo-preparations using cosmid and YAC clones for the simultaneous high resolution mapping of deletions in the dystrophin gene.

We report on multicolor fluorescence in situ hybridization protocols for the simultaneous visualization of deletion-prone regions for carrier detection of Duchenne/Becker (DMD/BMD) muscular dystrophy. Cosmid and yeast artificial chromosome (YAC) clones specific for preferentially deleted subregions of the dystrophin gene were labeled differentially and detected with three different fluorochromes using digital imaging microscopy. This approach allows for an assessment of the carrier status of female relatives even in families where no index patient is available. Cosmid and YAC clones, and different probe-generation protocols are compared with respect to their feasibility for carrier detection. The use of histone-depleted interphase nuclei (Halo-preparations) for deletion mapping is demonstrated and shown to have a resolution power of 5 kb.