Subtle overlapping deletions in the terminal region of chromosome 6q24.2-q26: Three cases studied using FISH

Interstitial deletions in the terminal region of chromosome 6 are rare. We describe three new cases with subtle interstitial deletions in the q24-q26 region of the long arm of chromosome 6. The karyotypes were analyzed at a 550 band level. Patient1 is a 9-month-old boy with an interstitial deletion, del(6)(q24.2q25.1), developmental delay, low birth weight, hypotonia, heart murmur, respiratory distress, craniofacial and genital anomalies. This is the first report of a case with deletion del(6)(q24.2q25.1). Patient 2 is a 17-year-old young man with an interstitial deletion del(6)(q25.1q25.3), developmental delay, short stature, mental retardation, autism, head, face, chest, hand and feet anomalies and a history of seizures. For the first time autism was described as a manifestation in 6q deletions. Patient 3 is baby boy with a de novo interstitial deletion, del(6)(q25.1q26), anomalies of the brain, genital organs, limbs and feet. This is the first report of a case with deletion, del(6)(q25.1q26). In all three patients, fluorescence in situ hybridization (FISH) using chromosome 6 painting probe ruled out an insertion. The ESR (6q25.1) and TBP (6q27) probes were used to confirm the breakpoints. Since TBP signal is present in all cases, it confirmed an interstitial deletion proximal to this probe. Patient 1 has a deletion of the ESR locus; Patient 2 and 3 have signals for the ESR locus on both chromosomes 6. Therefore the deletion in Patients 2 and 3 are between ESR and TBP loci distal to that of Patient 1. FISH validated the deletion breakpoints assessed by conventional cytogenetics. Am. J. Med. Genet. 87:17–22, 1999. © 1999 Wiley-Liss, Inc.     

Familial translocation t(10;14) (q26.1;q32.3): report of three offspring with 10q deletion and 14q duplication

We describe two brothers and a cousin with common clinical features, including mild mental retardation, motor delays, hypotonia with truncal ataxia, esotropia, and mild facial and hand dysmorphia. The initial routine chromosome study failed to detect any abnormality in the proband. Based on a high index of clinical suspicion, high-resolution chromosome studies were performed on the proband's parents. A small reciprocal translocation t(10;14) (q26.1;q32.3) was detected in the father. The breakpoint on the derivative chromosome 14 was further placed telomeric to the immunoglobulin heavy-chain gene cluster at the band q32.33 by fluorescence in situ hybridization. Studies of the proband and two affected paternal cousins revealed that each had inherited the same derivative chromosome 10 from their carrier parents. This unbalanced karyotype resulted from an adjacent-1 segregation of the 10;14 translocation.     

Mother to son transmission of del(1) (q42.1q42.3)

Familial transmission of cytogenetically visible autosome deletions is rare in humans. We describe here a case of mother to son transmission of an interstitial deletion of the distal long arm of chromosome one, breakpoints q42.1q42.3. This is the smallest described deletion of this region to date. © 2001 Wiley‐Liss, Inc.     

Second case report of del(4) (q25q27) and review of the literature

We report a malformed infant with a de novo interstitial deletion of 4q. This is the second patient reported with del(4) (q25q27). Although there are several common features such as marked hypotonia, cardiac abnormalities, cleft palate, and micrognathia noted in our case and that of Chudley et al. (1988), we conclude from our comparison of the seven previously reported cases involving deletions of bands 4(q25q27) that a specific phenotype cannot yet be described for this deletion.     

Interstitial deletion 2q14q21

A girl with multiple congenital anomalies and a tendency to severe pyogenic infections was found to have an interstitial deletion of chromosome band 2q14-q21. Unusual facial manifestations included enophthalmos, long philtrum, micrognathia, narrow forehead, prominent glabella, and depressed nasal bridge. Unilateral corneal clouding, with Peters-like anomaly; agenesis of the corpus callosum; brain atrophy; and heart, kidney, hand, and dermatoglyphic anomalies were additional findings. Eye anomalies were observed in five of 22 patients with deletions of chromosome 2q. In comparing these cases, it seems that deletions of bands 2q21 and 2q31 are variably associated with microphthalmia, corneal clouding, cataracts, and Peters anomaly. Measurement of protein C and interleukin-1 (IL-1) did not show a gene dose effect, but the pyogenic infections and low IgA found in this patient may reflect an abnormality of IL-1 not detectable by our methods.     

Clinical phenotype associated with terminal 2q37 deletion

Three children with deletions of the terminal portion of the long arm of chomosome 2 [del (2) (q37)] are described and their clinical findings compared to published cases of 2q terminal deletions. Common clinical findings include development delay, macrocephaly, frontal bossing, depressed nasal bridge and cardiac anomaly. Hypotonia and repetitive behavior are also seen during different times of development. The facial characteristics of children with 2q terminal deletions are not uniform, but development delay is a constant finding. Chromosomal analysis of such children using high resolution banding may uncover the diagnosis of a small chromosomal deletion.     

多发性骨髓瘤1q染色体异常与13q缺失的相关性研究

目的 探讨多发性骨髓瘤(multiple myeloma,MM)中13q14的缺失[del(13q14)]和1q染色体异常的相关性.方法 应用CD138单克隆抗体磁珠分选系统纯化48例初治MM患者的骨髓浆细胞,结合SpectrumorangeTM直接标记的位于13q14和1q12的序列特异性DNA探针和间期荧光原位杂交技术检测48例MM患者del(13q14)及1q染色体异常情况.结果 48例MM患者中,用D13S319探针检测,del(13q14)异常22例(45.8%);用CEP1探针检测.23例(47.9%)发现1q染色体异常.其中2例为1q缺失,21例为1q重复.22例伴有del(13q14)MM患者中16例出现1q染色体异常;26例未检测到del(13q14)MM患者中仅7例发现1q染色体异常.经X2检验两者间差异有统计学意义(X2=10.02,P＜0.01).结论 del(13q14)及1q染色体异常在MM中的发生率较高,两者间存在高度相关性.     

Interstitial deletion of chromosome 1 del (1) (q32 q42): case report and review of the literature

We describe the case of a female infant with multiple congenital anomalies who was found to have a de novo distal intestinal del (1) (q32 q42). The clinical features of other reports of similar deletions are briefly reviewed. No characteristic phenotype seems to be as yet definable due to the limited number of cases published.     

A case of de novo interstitial deletion of chromosome 5(q33q34)

The present paper describes a girl with a small de novo deletion of chromosome 5(q33q34). Fluorescence in situ hybridisation with locus specific probes was used to define the extent of this deletion. Clinical features in this patient are microcephaly, dysmorphic facial features such as epicanthus, small biparietal distance and retrognathia, four-finger lines on both hands and mild mental retardation.     

Autism and maternally derived aberrations of chromosome 15q

Of the chronic mental disabilities of childhood, autism is causally least well understood. The former view that autism was rooted in exposure to humorless and perfectionistic parenting has given way to the notion that genetic influences are dominant underlying factors. Still, identification of specific heritable factors has been slow with causes identified in only a few cases in unselected series. A broad search for genetic and environmental influences that cause or predispose to autism is the major thrust of the South Carolina Autism Project. Among the first 100 cases enrolled in the project, abnormalities of chromosome 15 have emerged as the single most common cause. The four abnormalities identified include deletions and duplications of proximal 15q. Other chromosome aberrations seen in single cases include a balanced 13;16 translocation, a pericentric inversion 12, a deletion of 20p, and a ring 7. Candidate genes involved in the 15q region affected by duplication and deletion include the ubiquitin-protein ligase (UBE3A) gene responsible for Angelman syndrome and genes for three GABA_A receptor subunits. In all cases, the deletions or duplications occurred on the chromosome inherited from the mother. Am. J. Med. Genet. 76:327–336, 1998. © 1998 Wiley-Liss, Inc.     

Interstitial 6q deletion and Prader-Willi-like phenotype

A third case of an interstitial deletion of the long arm of chromosome 6 with clinical features mimicking Prader-Willi syndrome (PWS) is presented. Although preliminary clinical evaluation in each case suggested PWS, further review revealed that the features in all three cases are not completely compatible with the characteristic findings in Prader-Willi syndrome. Furthermore, the deletions in the three cases do not show a consistent region of overlap. Consequently, no particular band or region in 6q can be defined as associated widi obesity. However, our findings confirm the suggestion of Villa et al. in 1995, that individuals with a PWS phenotype who are cytogenetically and molecularly negative for a deletion of 15q11-q13 should be examined for a deletion of 6q.     

Interstitial deletions 4q21.1q25 and 4q25q27: Phenotypic variability and relation to Rieger anomaly

We describe clinical and chromosomal findings in two patients with del(4q). Patient 1, with interstitial deletion (4)(q21.1q25), had craniofacial and skeletal anomalies and died at 8 months of hydrocephalus. Patient 2, with interstitial deletion (4)(q25q27), had craniofacial and skeletal anomalies with congenital hypotonia and developmental delay. These patients shared certain manifestations with other del(4q) patients but did not have Rieger anomaly. Clinical variability among patients with interstitial deletions of 4q may be related to variable expression, variable deletion, or imprinting of genes within the 4q region. © 1995 Wiley-Liss, Inc.     

Micromegakaryocytes in a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura

Thrombocytopenia or pancytopenia is frequently reported in patients with partial 11q deletion but there are no reports on bone marrow morphology of these patients. We report on a patient with partial deletion of the long arm of chromosome 11 [del(11) (q24.2qter)] and its classical clinical manifestations including chronic thrombocytopenic purpura in whom micromegakaryocytes were found in the bone marrow aspirate. This is the first report of the presence of micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate examination of the bone marrow of other patients with the 11q deletion may clarify whether the observation of micromegakaryocytes is common in these patients. Micromegakaryocytes may indicate a defect of development. Two genes for two DNA binding proteins that are likely to be involved in hematopoiesis map in the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear-factor-related-kB gene that maps to 11q24-q25. It is possible that these genes, when present in only one copy, result in thrombocytopenia or pancytopenia as observed in this patient. © 1996 Wiley-Liss, Inc.     

Unique de novo interstitial deletion of chromosome 17, del(17) (q23.2q24.3) in a female newborn with multiple congenital anomalies

We describe a newborn with a novel interstitial deletion of the long arm of chromosome 17 [del (17) (q23.2q24.3)] who died on day of life 17 during a recurrent apneic episode. Her phenotype included severe growth retardation, multiple facial anomalies, maldeveloped oralpharyngeal structures, and digital and widespread skeletal anomalies. This patient's phenotype was compared to two other reported patients with deletion 17q with minor clinical overlap consistent with a unique deletion. © 1995 Wiley-Liss, Inc.