Interstitial 3p deletion in a child due to paternal paracentric inserted inversion.

An infant with multiple anomalies and developmental delay during his first year was found to have an intersitital deletion of band p14 from the proximal short arm of chromosome 3. Examination of the father's chromosomes indicates an "inserted paracentric inversion" in chromosome 3 as the probable origin of the deletion in the child.     

Terminal deletion with stable acentric fragment of 1q in a child with congenital malformations

The terminal deletion with stable acentric fragment of 1q was found in a girl with multiple congenital malformations and severe mental retardation. The karyotype of both parents was normal, and the aberration appears de novo. The medium did not influence the expression of the aberration.     

Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line

p53 is a key modulator of a variety of cellular stresses. In human neuroblastomas, p53 is rarely mutated and aberrantly expressed in cytoplasm. In this study, we have identified a novel p53 mutant lacking its COOH-terminal region in neuroblastoma SK-N-AS cells. p53 accumulated in response to cisplatin (CDDP) and thereby promoting apoptosis in neuroblastoma SH-SY5Y cells bearing wild-type p53, whereas SK-N-AS cells did not undergo apoptosis. We found another p53 (p53DeltaC) lacking a part of oligomerization domain and nuclear localization signals in SK-N-AS cells. p53DeltaC was expressed largely in cytoplasm and lost the transactivation function. Furthermore, a 3'-part of the p53 locus was homozygously deleted in SK-N-AS cells. Thus, our present findings suggest that p53 plays an important role in the DNA-damage response in certain neuroblastoma cells and it seems to be important to search for p53 mutations outside DNA-binding domain.     

Interstitial deletion 1p as a result of a de novo reciprocal 1p;2p translocation

A 5-month-old female patient with psychomotor retardation and minor dysmorphisms is described. Cytogenetic analysis using high-resolution banding technique revealed an interstitial deletion of the short arm of one chromosome 1 (p21----p22.2) resulting from a de novo translocation t(1;2)(p22;p25).     

Unexpected death of a 12 year old boy with monosomy 1p36

Monosomy 1p36 may result in a clinically recognizable chromosomal microdeletion syndrome. We report the unexpected death of a 12 year old boy with mildly dysmorphic facial features, short stature at 138 cm (3rd centile), moderate mental retardation and a history of seizures, obesity, transient muscle weakness of the right arm and leg and episodes of transient atonic hemiparesis of the right side of the body. Despite the relatively few congenital anomalies and normal karyotype, the 1p36 deletion was suspected on clinical grounds and was demonstrated by fluorescent in situ hybridisation (FISH). Two months after diagnosis and following a short history of a mild upper airway infection, high fever and severe diarrhea, the patient had a massive circulatory shock and asystolia, resulting in deep coma, brain edema, apallic syndrome and death. To our knowledge there has been no previous report of episodes of transient unilateral muscle weakness and atonic hemiparesis, circulatory shock and sudden death associated with monosomy 1p36.     

CHD5 is a tumor suppressor at human 1p36

Cancer gene discovery has relied extensively on analyzing tumors for gains and losses to reveal the location of oncogenes and tumor suppressor genes, respectively. Deletions of 1p36 are extremely common genetic lesions in human cancer, occurring in malignancies of epithelial, neural, and hematopoietic origin. Although this suggests that 1p36 harbors a gene that drives tumorigenesis when inactivated, the identity of this tumor suppressor has remained elusive. Here we use chromosome engineering to generate mouse models with gain and loss of a region corresponding to human 1p36. This approach functionally identifies chromodomain helicase DNA binding domain 5 (Chd5) as a tumor suppressor that controls proliferation, apoptosis, and senescence via the p19(Arf)/p53 pathway. We demonstrate that Chd5 functions as a tumor suppressor in vivo and implicate deletion of CHD5 in human cancer. Identification of this tumor suppressor provides new avenues for exploring innovative clinical interventions for cancer.     

First trimester abortions associated with a translocation t(1;20)(p36;p11)

Summary A large family with a high rate of spontaneous abortions was found also to have a high incidence of a reciprocal translocation.     

Terminal 7p deletion and 1;7 translocation associated with craniosynostosis

Summary A female infant with presumptive deletion of the 7p2 region and an unusual translocation between a part of the short arm of chromosome 1 and a deleted chromosome 7 is described. The patient showed congenital craniosynostosis of the coronal and metopic sutures; marked turricephaly; hypotelorism; deeply cleft palate; shallow orbits with prominent bulging eyes; a depressed nasal bridge; anteverted nostrils; short hands with broad thin fingers and elongated thumbs; a mild talipes calcaneovalgus deformity of the feet; a systolic murmur due to a small VSD; and psychomotor retardation. The child died of bronchopneumonia at 10 weeks of age. The parents are chromosomally normal.     

A 3p deletion syndrome in a child with both del(3)(p25-->pter) and dup(17)(q23-->qter).

A child with monosomy for the distal part of the short arm of chromosome 3 (3p25-->pter) and trisomy for the terminal portion of the long arm of chromosome 17 (17q23-->qter) is presented. This unbalanced karyotype was derived from a balanced reciprocal 3p/17q translocation in the phenotypically normal mother. Main clinical features in the proband included growth and mental retardation, hypotonia, hirsutism, micro/brachycephaly, triangular face, synophris, broad and full nose, long philtrum, narrow upper lip, low set, posteriorly turned ears, anteriorly placed anus and congenital heart defect (Tetralogy of Fallot). Most of these clinical manifestations have been constantly reported in previous cases with terminal 3p deletion.     

Pure distal 9p deletion in a female infant with cerebral palsy

We report cytogenetic and molecular characterization of a 15.63-Mb pure distal deletion of chromosome 9p (9p22.3-->pter) in a l 1/2-year-old female infant with cerebral palsy and diffuse cerebral dysfunction. The deletion is of paternal origin and encompasses the genes of ANKRDS15, DOCK8, FOXD4 and VLDLR. We discuss the genotype-phenotype correlation in this case with neurological dysfunction and a distal 9p deletion of paternal origin.     

Translocation involving 1p and 17q is a recurrent genetic alteration of human neuroblastoma cells.

Human neuroblastoma cells often are monosomic for the distal portion of 1p (1p36). We report that the deleted 1p material in cells of neuroblastoma lines is preferentially replaced by material from chromosome 17, resulting from an unbalanced 1;17 translocation. Chromosome 17 often acquires instability, followed by the integration of fragments into various marker chromosomes. As a consequence, 17q material can increase over 17p material. The nonrandom frequency of 1;17 translocations appears to indicate an as-yet-undefined contribution to neuroblastoma development.     

Identification of a deletion in the adenosine deaminase gene in a child with severe combined immunodeficiency

A patient with adenosine deaminase-deficient severe combined immunodeficiency is described whose defect is secondary to deletion of a portion of the ADA structural gene. In Southern analyses, DNA from this patient does not hybridize to a genomic probe that includes the 3' end of exon 1. This implies that both his parents are heterozygous for deletions of exon 1 sequences. Consistent with this finding, the patient has no detectable adenosine deaminase mRNA by Northern analysis. This is the first report of a deletion mutation as the cause of adenosine deaminase deficiency.     

14q terminal deletion: prenatal diagnosis in a child with severe congenital anomalies

A fetal patient presented at 27.3 weeks of gestation with polyhydramnion. Ultrasound examination showed enlarged cerebral ventricles, abnormal position of the fingers and abnormal external genitals. Chromosome studies in chorionic villus material were normal male: in cultured amniocytes a distal deletion 14q32 was demonstrated and confirmed by FISH analysis. The baby was born at 37 weeks and died spontaneously during labour. This is the first report of prenatal diagnosis of a terminal 14q deletion.     

A novel de novo deletion of chromosome 7 [46,XX,del(7)(p14.2 p15.1)] in a child with feeding problems

The phenotype and severity of symptoms associated with deletions on chromosome 7 are directly proportional to the size of the deleted segment. Distal and interstitial deletions have been described in 40 cases. In this report the authors aim to report a child with a novel de novo interstitial deletion on chromosome 7, with the following karyotype: 46,XX,del(7)(p14.2 p15.1). We described a female, born at 38 weeks with intrauterine growth restriction and feeding problems with episodes of cyanosis after feedings and failure to thrive. Physical examination showed low implantation of ears, hypertelorism, oblique palpebral fissures, retrognathia, and palate ogived, with insertion anomalies of the toes, poor facial expression and mild axial hypotonia. Transfontanelar ultrasound, magnetic resonance imaging, bronchofibroscopy and metabolic studies were normal. She was hospitalized until the 32nd day of life. She started speech therapy and presented improvements in swallowing. The percutaneous endoscopic gastrostomy was removed at 36 months. She had recurrent urinary tract infection with normal dimercaptosuccinic acid but with a vesicoureteral reflux (grade III). Imagiological studies revealed a bilateral osteonecrosis of femoral epiphysis (Legg-Calvé-Perthes disease). Currently (6years-old), she is being normally fed (body mass index=15.8kg/m(2)). Her weight is 16.4kg (3rd centile) and length is 105cm (3rd to 5th centiles). She has a mild delay of psychomotor development impairment and some speech problems. This is the first case report of a patient with this de novo small interstitial deletion on chromosome 7. This rare chromosomal abnormality was associated with severe feeding problems in the first years of life.     

Mewing cry in a child with the partial deletion of the short arm of chromosome No. 4

Summary A case is presented of partial deletion of the short arm of the chromosome No. 4, but with a mewing cry, typical of the 5p — deletion syndrome. The clinical examination revealed similar features to those described in other cases of 4p — deletion, namely low birth weight, hypertelorism, facial asymmetry, failure to thrive, mental retardation, beak-shaped nose, low set ears, broad nasal bridge, skeletal anomalies and hypotony. The mewing character of the voice was confirmed by analysis of the voice spectrum. The deleted chromosome was identified by the measurement technique.