Terminal deletion(4)(q33) in a male infant

The deletion of 4q31→qter is associated with a recognizable "4q^- syndrome". It has been proposed that the much rarer deletion 4q33→qter causes a milder phenotypic expression of the 4q^- syndrome. We present the second case, the first male, with the latter deletion and compare his clinical features to those of other 4q^- patients.     

Del(10)(q22.3q24.1) associated with juvenile polyposis

Juvenile polyps are the most frequent gastrointestinal polyps with a malignant potential for which the genetic basis is unknown. Juvenile polyps, with a normal epithelium but hypertrophic lamina propria, are histologically quite distinct from adenomatous polyps which have dysplastic changes in epithelial nuclei. Furthermore, the adenomatous polyposis coli (APC) gene on Chr 5, mutated somatically in adenomatous polyps and mutated in the germline of patients with familial adenomatous polyposis, is not linked to hereditary juvenile polyposis. We provide the first report indicating that a tumor suppressor gene associated with juvenile polyposis may be located at 10q22.3q24.1. Cytogenetic studies of a patient with juvenile polyposis and multiple congenital abnormalities of the head, extremities, and abdomen revealed a de novo interstitial deletion of Chr 10 as the only defect, del(10)(10q22.3q24.1). Am. J. Med. Genet. 70:361–364, 1997. © 1997 Wiley-Liss, Inc.     

Del(1)(q23) in a patient with Hutchinson-Gilford progeria

A 9-year-old patient with the classical clinical picture of Hutchinson-Gilford progeria (HGP) is described. The karyotype shows a 46,XY,del(1)(q23) constitution. Our findings suggest that the interval 1q23 may play a roll in the etiology of HGP. A perturbation in glycosylation in connective tissue has been demonstrated in patients with this condition. This abnormality may be due to a defect in the UDP-galactose:beta-N-acetylglucosamina-beta-1,4-galactosyltransferase 3 (B4GALT3) gene that has been mapped in the interval 1q21-23. The cytogenetical analyses of this patient suggest that the B4GALT3 gene could be involved in the pathogenesis of HGP.     

Familial t(8;15)(p23.3;q22.3): report of two cases with dup(15) (q22.3----qter).

Two affected first cousins with duplication of 15(q22.3----qter) are reported. This resulted from a familial t(8;15)(p23.3;q22.3) translocation. The findings in these patients are compared with each other and with six other published cases. Anthropometric and dermatoglyphic findings are summarised.     

Del(14)(q22.1q23.2) in a patient with anophthalmia and pituitary hypoplasia

Only few cases with an interstitial deletion of chromosome 14 have been described so far. We report on a 21-month-old girl with an interstitial deletion of the long arm of chromosome 14, del(14)(q22.1q23.2). She presented with bilateral anophthalmia, absent left external auditory canal, facial asymmetry, microretrognathia, hypotonia, and psychomotor retardation. Skeletal X-rays showed lambdoid craniosynostosis, a very small sella turcica and cervical vertebral anomalies. Brain MRI showed the absence of the optic chiasm, an hypoplastic pituitary gland, and cortical atrophy. No cardiac or abdominal malformations were found. Two other patients with a similar deletion, (del(14)(q22.1q23) and del(14)(q22.1q22.3)), are described. Both presented with bilateral anophthalmia and absent pituitary or hypogonadism. These three cases suggest that the region 14q22 is important for eye and pituitary development. Interestingly, the human BMP-4 gene, a member of the TGF-β superfamily, maps to 14q22-q23 and may play a role in pituitary and eye development. Am. J. Med. Genet. 77:162–165, 1998. © 1998 Wiley-Liss, Inc.     

Interstitial deletion del(2)(q24q31) with a phenotype similar to del(2)(q31q33)

A 3 3/12-year-old girl with multiple anomalies is reported. An interstitial deletion del(2)(q24q31) was demonstrated. There is considerable overlap of symptoms in cases with del(2)(q31q33), which are reviewed.     

A report of a child with a deletion (9)(q34.3): a recognisable phenotype?

We report a case of a male infant who presented with congenital anomalies and was found to have a de novo deletion in the terminal region of the long arm of chromosome 9. He died at the age of 17 weeks of cardiorespiratory failure owing to RSV positive bronchiolitis. A review of previously published reports documented one previous report of a patient with a deletion of (9)(q34.3) and multiple congenital anomalies. Comparison with the previously reported case suggests that the phenotype observed constitutes a clinically recognisable pattern of malformations.     

Isochromosome (17)(q10) and translocation (4;12)(q12;p13) in a child with acute myeloid leukemia.

Isochromosome 17q is a commonly observed cytogenetic aberration in hematologic malignancies. Isolated isochromosome 17q usually presents as a marker of a chronic myeloid disorder, with a high propensity for transformation into acute nonlymphoblastic leukemia (ANLL). t(4;12)(q11-12;p13) is a recently described translocation, associated with ANLL, predominantly in adults. In this article, we present a case of acute myeloblastic leukemia (AML) in a 14-year-old female in which i(17q) and t(4;12)(q12;p13) were found in the leukemic clone at diagnosis. We briefly review the literature and hypothesize as to the significance of the coexistence of these cytogenetic changes.     

Del(1)(q23) in a patient with Hutchinson‐Gilford progeria

A 9‐year‐old patient with the classical clinical picture of Hutchinson‐Gilford progeria (HGP) is described. The karyotype shows a 46,XY,del(1)(q23) constitution. Our findings suggest that the interval 1q23 may play a roll in the etiology of HGP. A perturbation in glycosylation in connective tissue has been demonstrated in patients with this condition. This abnormality may be due to a defect in the UDP‐galactose:β‐N‐acetylglucosamina‐β‐1,4‐galactosyltransferase 3 (B4GALT3) gene that has been mapped in the interval 1q21‐23. The cytogenetical analyses of this patient suggest that the B4GALT3 gene could be involved in the pathogenesis of HGP. © 2002 Wiley‐Liss, Inc.     

Del(14)(q22) in diffuse B-cell lymphocytic lymphoma

Some recurrent chromosomal abnormalities have recently been found to be associated with distinctive histologic subtypes of non-Hodgkin's lymphoma (NHL). In a study of 62 patients with NHL whose karyotypes was determined at diagnosis, 3 patients were found to have a deletion of the long arm of chromosomes 14 at band 22 (del[14][q22]). All had a diffuse lymphoma with generalized lymphadenopathy and bone marrow involvement. All three lymphomas were of B-cell origin, as shown by the presence of surface immunoglobulin and monoclonal antibody phenotyping. For each patient, a trisomy 12 was associated with del(14)(q22) in a clone. These data suggest that del(14)(q22), perhaps in association with trisomy 12, could identify a subtype of NHL and that band 22 of chromosome 14 may be implicated in the B-cell ontogeny.     

Five children with del (2)(q31q33) and one individual with dup (2)(q31q33) from a single family: review of brain, cardiac, and limb malformations

Five matings to a dir ins (6;2)(q16;q31q33) carrier have produced a high frequency (42%) of offspring with unbalanced karyotypes. Five children have the derivative chromosome 2 resulting in del (2)(q31q33) and one individual received the derivative chromosome 6 leading to dup (2)(q31q33). The findings associated with the deletion include pre- and postnatal growth retardation, developmental delay, minor facial anomalies, seizures, complex structural heart defects, and limb deficiency. Autopsy of one individual showed complex brain malformations including hydrocephalus secondary to obstruction of the foramina of Monro, extensive heterotopias and polymicrogyria, and an unusual form of total anomalous pulmonary venous return. We compare the findings in these children to those of previously reported cases and construct an overview of the range of anomalies. Apparently, no other individual with dup (2)(q31q33) has been described. We compare the physical peculiarities of our patient with those of individuals with duplications of overlapping regions of 2q.     

Terminal deletion (14)(q32.3): a new case.

A mildly dysmorphic, 2 year old girl with mental retardation was found to have a small de novo terminal deletion of the long arm of chromosome 14, del(14)(q32.3). She was found to have features in common with two previous terminal deletion cases and particularly with the well documented ring 14 syndrome, although seizures, a characteristic feature of ring 14, were notably absent.     

A rec(4) dup 4p inherited from a maternal inv(4)(p15q35): case report and review

A rec(4) dup 4p inherited from a maternal inv(4)(p15q35) was detected in a four-year-old girl with malformations, developmental delay, and behavioral problems that resemble those for trisomy 4p. A review of eight other liveborns with rec(4) dup 4p shows that about 40% of them also have manifestations in common with trisomy 4p, but the rest have a variable spectrum of malformations. Overall, the rec(4) dup 4p phenotype is not specific, and a diagnosis would not have been feasible without cytogenetic studies. This lack of a clinically recognizable phenotype could reflect the effects of the variable sizes of deletions of 4q, molecular differences in the break points, or the known variable expression of trisomy 4p. The fact that 79% of the recombinants in the offspring of inv(4)(p13-p15q35) carriers are rec(4) dup 4p suggests that meiotic recombination favors its generation or that rec(4) dup 4q are more lethal in utero.     

Child with velocardiofacial syndrome and del (4)(q34.2): another critical region associated with a velocardiofacial syndrome-like phenotype

We report on a child with congenital heart disease (atrial septal defect, ventricular septal defect, pulmonic stenosis), submucosal cleft palate, hypernasal speech, learning difficulties, and right fifth finger anomaly manifestations, consistent with velocardiofacial syndrome (VCFS); however, cytogenetic analysis demonstrated a small terminal deletion of the segment 4q34.2 to 4qter. Fluorescent in situ hybridization did not identify a deletion of the critical region associated with VCFS. In previously reported 4q deletions with a breakpoint distal to 4q34.2, no cardiac defects or cleft of palate were reported. Our patient has a deletion of 4q34.2 to 4qter and has palate and cardiac involvement and minor learning difficulties, which implies that genes involved in heart and palate development lie distal to 4q34.2, and that the critical region for more severe mental retardation on 4q may reside proximal to 4q34.2. These results suggest that a distal 4q deletion can lead to a phenotype similar to VCFS and emphasizes the importance of searching for other karyotype abnormalities when a VCFS-like phenotype is present and a 22q deletion is not identified.     

Interstitial deletion, del(4)(q33q35.1), in a mother and two children.

The inheritance of autosomal deletions from affected parents has only rarely been reported. We report an unbalanced interstitial deletion, del(4)(q33q35.1), in a mother and two male offspring. The mother and older sib are mentally retarded but have only mild dysmorphic features. The younger sib, at five months, is showing signs of developmental delay. All three patients show some abnormalities in common with cases that have terminal deletions of 4q with breakpoints at 4q33, but in general exhibit less severe abnormalities. The family illustrates the importance of detailed cytogenetic analysis of children with developmental delay who do not display major dysmorphic features.     

A case of papillary meningioma with a t(1;4)(q44;q21)

We report the results of cytogenetic analyses of three cases of meningiomas. The first case, a papillary meningioma, showed only one cytogenetic abnormality, 46,XX,t(1;4)(q44;q21). In contrast, the other two benign fibroblastic meningiomas showed loss of chromosome 22. Loss and/or rearrangement of chromosomes other than chromosome 22 appears to be associated with a more aggressive clinical course. It is suggested that a sole cytogenetic abnormality with a normal chromosome 22 indicates an atypical nature of meningioma.