Interstitial deletion of chromosome 13 and associated congenital anomalies

Summary An interstitial deletion of chromosome 13 with breakpoints at 13q22 and 13q32 is presented. The clinical findings associated with this deletion are discussed in relation to the correlations of specific chromosomal bands with constellations of congenital defects as described by Niebuhr and Ottosen (1973), Niebuhr (1977), Lewandowski and Yunis (1975), and Noel et al. (1976).     

An adult patient with a distal interstitial 14q deletion: clinical report and literature review

We report a patient with an interstitial 14q32.1-->q32.3 deletion and review the literature. The adult patient presented with moderate mental retardation, a friendly behavior and a non-specific phenotype. The deletion seemed to be terminal but with FISH probes appeared to be interstitial. Comparison with other 14q terminal and interstitial deletion patients reported in literature and those with a ring 14 chromosome is given.     

Deletion of 13q in two patients with retinoblastoma,one probably due to 13q- mosaicism in the mother

Summary We examined the peripheral blood chromosomes of eight patients with retinoblastoma. In two of them an interstitial deletion of 13q was found. The breakpoints were determined as follows: case 1, 13q1221; case 2, 13q1231. In both cases, band 13q14 was deleted. In case 2 the lymphocytes of the mother showed the identical interstitial 13q deletion in 3 of 100 mitoses, thus raising the possibility of maternal origin of the 13q deletion in a child. In one patient, retinoblastoma was unilateral; in the other, bilateral. Both patients were mentally retarded.     

Interstitial 1q42-q44 deletion defined by FISH in a short-lived female

We report a female newborn with a de novo 1q4 deletion ascertained by G bands but refined as an interstitial one by FISH with a subtelomeric 1q probe; hence, the final karyotype was 46,XX,del(1)(q42q44).ish subtel1q x 2. She presented a few typical features of the del(1q42) syndrome. Additionally, she showed occipital skin aplasia, interauricular communication, and intestinal perforation-obstruction and she died at 24 days of age. This observation illustrates the clinical variability of the syndrome as well as the occasional reduced survival. The redefinition by molecular cytogenetics of a terminal deletion as an interstitial one suggests that interstitial deletions are more common than reported by classic cytogenetics and can partially account for the phenotypic variability in some deletion syndromes.     

Chromosome 13 long arm interstitial deletion associated with features of Noonan phenotype

A 22-year-old Caucasian mildly retarded male presented with facial features of high nasal bridge, prominent supraorbital ridges, some malar hypoplasia, prognathism, short philtrum, and prominent full lips associated with shortness of stature, nuchal webbing, and esotropia. His cardiac exam and genital development were normal. The diagnosis of Noonan syndrome had been previously entertained. A chromosome analysis revealed an interstitial deletion of a chromosome 13 at (q21.32q22.3).     

Phenotypical characterization of 13q deletion syndrome: Report of two cases

Patients with 13q deletion syndrome are characterized with different phenotypical features depending on the size and location of the deleted region on chromosome 13. These patients fall into three groups: In Group 1, deleted region is in the proximal and does not extend into q32; in Group 2, deleted region involves proximal to the q32 and in Group 3 q33-q34 is deleted. We present two cases with 13q syndrome with two different deleted region and different severity on clinical features: One case with interstitial deletion belongs to the Group 1 with mild mental retardation and minor malformations and the other case with terminal deletion belongs to Group 3 with moderate to severe mental retardation and major malformations.     

Partial monosomy of long arm of chromosome 4 due to interstitial deletion

Summary A child with congenital malformations and a de novo interstitial deletion of the long arm of chromosome 4 is described. Detailed analysis by G banding revealed the loss of the whole of band q21 and part of bands q13 and q22. The clinical abnormalities are quite dissimilar from those features described in other cases of partial 4q monosomy, which generally appear to result from the deletion of more distally placed segments of the chromosome.     

Interstitial deletion of chromosome 15: two cases

Summary Two cases of interstitial deletion of chromosome 15 with similar clinical features are presented. In one case, assay of hexosaminidase A enabled us to confirm that the structural gene is located between 15q22 and 15q25 and that it is included in the deletion.     

Presumptive long arm deletion of chromosome 8: a new syndrome?

Summary This communication describes an infant with growth and psychomotor retardation and severe congenital malformations, who was found to have an interstitial deletion of the long arm of chromosome 8: 46,XY,del(8) (q13q22). Comparison with the only other previously reported patient with a deletion of a similar chromosomal segment suggested that deletion of the long arm of chromosome 8 may constitute a clinically recognizable syndrome.     

Interstitial deletion of chromosome 13 involving the region 13q14

Summary A patient with an interstitial deletion 13q14 is described who has decreased erythrocyte esterase D activity and who has not developed a retinoblastoma.     

Cytogenetic findings in a prospective series of patients with DiGeorge anomaly.

High-resolution cytogenetics analysis of peripheral blood lymphocytes was done prospectively on 27 of 28 patients with features of DiGeorge anomaly. Twenty-two patients (81%) had normal chromosome studies with no detectable deletion in chromosome 22. Five patients (18%) had demonstrable chromosome abnormalities. Three patients had monosomy 22q11, one due to a 4q;22q translocation, one due to a 20q;22q translocation, and one due to an interstitial deletion of 22q11. One patient had monosomy 10p13, and one patient had monosomy 18q21.33, although the latter had subsequent resolution of T-cell defects. These findings are consistent with the heterogeneity of DiGeorge anomaly but confirm the association with monosomy 22q11 in some cases. However, monosomy 10p13 may also lead to this phenotype. Because of these associated chromosome findings, cytogenetic analyses should be done on patients with suspected DiGeorge anomaly. This is particularly important since many of the abnormalities involving chromosome 22 are translocations that can be familial with a higher recurrence risk. Since only one subtle, interstitial deletion of chromosome 22 was observed, it is not clear whether high-resolution cytogenetic analysis is cost beneficial for all such patients.     

Clinical and genomic evaluation of 201 patients with Phelan–McDermid syndrome

This study is the first to describe age-related changes in a large cohort of patients with Phelan–McDermid syndrome (PMS), also known as 22q13 deletion syndrome. Over a follow-up period of up to 12 years, physical examinations and structured interviews were conducted for 201 individuals diagnosed with PMS, 120 patients had a focused, high-resolution 22q12q13 array CGH, and 92 patients’ deletions were assessed for parent-of-origin. 22q13 genomic anomalies include terminal deletions of 22q13 (89 %), terminal deletions and interstitial duplications (9 %), and interstitial deletions (2 %). Considering different age groups, in older patients, behavioral problems tended to subside, developmental abilities improved, and some features such as large or fleshy hands, full or puffy eyelids, hypotonia, lax ligaments, and hyperextensible joints were less frequent. However, the proportion reporting an autism spectrum disorder, seizures, and cellulitis, or presenting with lymphedema or abnormal reflexes increased with age. Some neurologic and dysmorphic features such as speech and developmental delay and macrocephaly correlated with deletion size. Deletion sizes in more recently diagnosed patients tend to be smaller than those diagnosed a decade earlier. Seventy-three percent of de novo deletions were of paternal origin. Seizures were reported three times more often among patients with a de novo deletion of the maternal rather than paternal chromosome 22. This analysis improves the understanding of the clinical presentation and natural history of PMS and can serve as a reference for the prevalence of clinical features in the syndrome.     

Characterization of an interstitial deletion del(13)(q22q32) using microdissection and sequential FISH and G-banding

The objective of this study was to delineate a chromosome 13 abnormality and establish its clinical correlation by using molecular cytogenetics procedures. A newborn boy presented with clinical findings, including mild symmetric intrauterine growth retardation (IUGR), small ears with thickened helices, a scalp lesion, short fifth fingers, missing toes, and talipes equinovarus. Routine G-banding of cultured peripheral blood cells revealed that the patient had one abnormal and shortened chromosome 13, but uncertainty remained as to whether the abnormality was the result of an interstitial deletion or a translocation. Thirteen copies of G-banded abnormal chromosomes 13 were isolated with microdissection and amplified with PCR using degenerate oligonucleotide primers. Fluorescence in situ hybridization (FISH) of the PCR product to normal metaphases showed one pair of acrocentrics hybridized, more or less uniformly, along the length of the long arm with an unhybridized gap in the distal region, indicative of an interstitial deletion. Sequential FISH and G-banding of the same chromosome preparations conclusively demonstrated that the deleted segment was 13q22-q32. Four cases of del(13)(q22q32) have been previously reported. The common findings in all five cases, including the present one, are psychomotor and growth retardation, as well as hand and foot anomalies.     

Coincidence between fragile site expression and interstitial deletion of chromosome 11 in a case of myelofibrosis

Summary Cytogenetic examination of multiple peripheral blood cultures of a patient with myelofibrosis with myeloid metaplasia revealed the presence of an interstitial deletion of the long arm of chromosome 11, del(11)(q13q21). A folic acid dependent fragile site fra(11)(q13) was found in about 12% of the cells. The possible correlation between constitutional fragile site and acquired chromosomal alteration is discussed briefly.     

Identical twins with deletion 16q syndrome: Evidence that 16q12.2-q13 is the critical band region

Summary An interstitial deletion of the long arm of chromosome 16 has been identified in identical twins. These patients are strikingly similar phenotypically to previously reported cases of deletion 16q syndrome but differ chromosomally in that their deletion involves the 16q12.2-q13 rather than the 16q21. We propose that the 16q12.2-q13 is the critical region in the production of this rare but distinctive phenotype.     

Retinoblastoma,gross internal malformations,and deletion 13q14→q31

Summary A male patient with an interstitial deletion 13q14q31 is described. Our necropsy findings included a left retinoblastoma and several gross internal malformations. In this paper we reaffirm that band 13q14 is involved in cases of retinoblastoma and we propose, after studying accompanying cases of total or partial long arm trisomies 13, that the loss of specific 13q bands, from 13q14 to 13q31 is responsible for the congenital defects we are describing.     

Interstitial deletion 13q syndromes: A report on two unrelated patients

Summary A partial monosomy 13 by interstitial deletion was found in the complement of two patients with mental retardation and mild dysmorphic features. Neither of the patients had a retinoblastoma, even though the second patient had a 13q14 deletion. The karyotype-phenotype correlation in the two patients suggests the need to reconsider the clinical profile of these rare chromosomal syndromes in a large series of subjects.     

Centric fission of chromosome 7 with 47,XX,del(7)(pter----cen::q21----qter)+cen fr karyotype in a mother and proximal 7q deletion in two malformed newborns

In the present paper we report a characteristic pattern of external and internal malformations in two male siblings with proximal 7q interstitial deletion as the unbalanced product of a rearranged chromosome 7 in the mother with karyotype 47,XX,del(7)(pter----cen::q21----qter),+fr. The interstitial 7q deletion in the mother included centromeric fission, break at 7q21 and preservation of the proximal q arm fragment.     

Aniridia-Wilms' tumor association: evidence for specific deletion of 11p13.

A 7-year-old boy with aniridia, Wilms' tumor, and mental retardation, previously reported as having an interstitial deletion of the short arm of chromosome 8 resulting from a t(8p+;11q-) translocation (Ladda et al., 1974), has been restudied using high-resolution trypsin-Giemsa banding of prometaphase chromsomes. The results revealed a complex rearrangement with four break points in 8p, 11p, and 11q, leading to a net loss of an interstitial segment of 11p (region p1407 yields p1304) but not of 8p. His red blood cells contained normal activities of glutathione reductase (gene on 8p) and lactate dehydrogeanse A (gene on 11p12), indicating a gene dosage consistent with the chromosomal findings. The revised interpretation of this case agrees with seven others reported as having aniridia and interstitial 11p deletions in establishing the distal half of band 11p13 as the site of gene(s) which lead to aniridia and predispose to Wilms' tumor if present in a hemizygous state. Possible relationships between heterozygous deletion of specific chromosomal bands 11p13 and 13q14 and the autosomal dominant disorders aniridia, Wilms' tumor, and retinoblastoma, respectively, are discussed.     

Hereditary retinoblastoma and 13q--mosaicism

Mosaicism for a 13q interstitial deletion was found in a minor fraction of peripheral blood lymphocytes in a 10-month-old girl affected with bilateral retinoblastoma. The tumor was inherited from the unilaterally affected father.