Deletions of different segments of the long arm of chromosome 4

We report the clinical and chromosomal findings in 8 patients with deletions of the long arm of chromosome 4. Four of these patients appear to have terminal deletions beginning in band 4q31, and therefore, lack the digital 1/3 of the long arm of chromosome 4. We confirm that deletion of 4q31→qter causes a recognizable syndrome, and we further define the phenotype of that syndrome. A 5th patient has a shorter terminal deletion, ie, 4q33→qter. This deletion causes a milder phenotypic expression than that seen in the severe 4q terminal-deletion syndrome. The remaining 3 patients have interstitial deletions of the long arm of the 4th chromosome, including segments 4q21.1→q25, 4q21.3→q26, and 4q27→q31.3. The phenotypic expression noted in these patients is variable and differs from the 4q terminal-deletion syndrome.     

Deletions of the long arm of chromosome 10

Patients with a partial deletion of the long arm of chromosome 10 are rare. We report eight new cases involving various segments of 10q: one terminal deletion (10q26), four (8;10) translocations resulting in terminal deletions (10q26) and duplications (8q24.3), a de novo interstitial deletion (10q23), an interstitial deletion due to a (10;13) translocation (10q11.2----10q22.1), and a ring (10p15----10q26).     

Monosomy 6q: report on four new cases

We report on four patients with partial monosomy of the long arm of chromosome 6: two children presenting with an interstitial deletion del(6)(q14q16), the two others presenting with a terminal deletion del(6)(q25qter). These patients are compared with previous reports in the literature: 16 cases of terminal deletion and 17 cases of interstitial deletion. The deletions most often occur de novo. Mental retardation is always described. Dysmorphic facial features range between minor and major. There may be associated visceral abnormalities. After comparing the size and the localisation of the deletions with clinical data, we are now able to suggest a clinical localisation on chromosome 6.     

Molecular analysis of three patients with interstitial deletions of chromosome band 14q31.

Two patients and one three generation family with interstitial deletions of distal chromosome band 14q31 are described. The deletions were initially identified by chromosome analysis; we have used highly informative simple sequence repeat polymorphisms to define the deletions at the molecular level. This analysis also establishes the parental origin of the deleted chromosome. One of the patients was initially described as having a terminal deletion of chromosome 14 from 14q31 to 14qter; we show here that this child has instead an interstitial deletion of band 14q31. The smallest deletion involves a single anonymous DNA marker and is associated with an almost normal phenotype. The two patients with larger deletions have phenotypes similar to those seen in previously described cases of interstitial deletions of chromosome 14, including minor dysmorphic features and developmental delay. Delineation of these deletions allows the ordering of markers within the 14q31 region, in which the gene for the degenerative neurological disorder Machado-Joseph disease is localised.     

Monosomy and trisomy of 15q24→qter in a family with a translocation t(6;15)(P25;q24)

A child with multiple anomalies, including growth retardation, a left-sided diaphragmatic hernia with lung hypoplasia, and cerebral malformations is described. Cytogenetic investigation demonstrated a deletion of the distal part of one chromosome 15, del(15)(q24qter), an aberration not previously described. Family studies revealed that the mother had a balanced translocation, t(6;15)(p25;q24). Two of her subsequent pregnancies resulted in abortions after prenatal diagnosis: one fetus was trisomic for 15q24→qter, while the other had monosomy 15q24→qter and a left-sided diaphragmatic hernia similar to the first child.     

Cryptic subtelomeric translocations in the 22q13 deletion syndrome

Cryptic subtelomeric rearrangements are suspected to underlie a substantial portion of terminal chromosomal deletions. We have previously described two children, one with an unbalanced subtelomeric rearrangement resulting in deletion of 22q13→qter and duplication of 1qter, and a second with an apparently simple 22q13→qter deletion. We have examined two additional patients with deletions of 22q13→qter. In one of the new patients presented here, clinical findings were suggestive of the 22q13 deletion syndrome and FISH for 22qter was requested. Chromosome studies suggested an abnormality involving the telomere of one 22q (46,XX,?add(22)(q13.3)). FISH using Oncor D22S39 and Vysis ARSA probes confirmed a terminal deletion. A multi-telomere FISH assay showed a signal from 19qter on the deleted chromosome 22. Results were confirmed with 19qtel and 22qtel specific probes. The patient is therefore trisomic for 19qter and monosomic for 22qter. The patient''s mother was found to have a translocation (19;22)(q13.42;q13.31). We also re-examined chromosomes from two patients previously diagnosed with 22q deletions who were not known to have a rearrangement using the multi-telomere assay. One of these patients was found to have a derivative chromosome 22 (der(22)t(6;22)(p25;q13)). No evidence of rearrangement was detected in the other patient. Thus we have found the 22q13 deletion to be associated with a translocation in three of four patients. This report illustrates the usefulness of examining patients with hypotonia, severe language delay, and mild facial dysmorphism for this syndrome and suggests that most of these deletions may be unbalanced subtelomeric rearrangements.     

Detection of an unexpected subtelomeric 15q26.2 --> qter deletion in a little girl: clinical and cytogenetic studies

Unlike the small proximal 15q deletions causing Prader-Willi and/or Angelman syndrome, distal deletions of the terminal long arm of chromosome 15 have rarely been described. To the best of our knowledge, only four patients with a pure terminal 15q deletion have been documented in the literature. We report here on an unexpected abnormal hybridization pattern for the 15q specific subtelomeric control probe (clone 154P1) of the commercial SNRPN probe in a girl referred for suspicion of Angelman syndrome. Investigation by fluorescent in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones defined a partial monosomy 15q26.2 --> 15qter for a minimal critical region of approximately 5.7 Mb, which is the most distal de novo 15qter deletion reported to date. All the de novo 15qter deletion cases, including ours, presented with pre- and post-natal growth retardation related to the loss of one copy of the IGF1R gene. Based on the comparaison with the previous published cases and owing to the clinical phenotype of our patient, we define a new subtelomeric 15qter syndrome which would be characterized by intrauterine growth retardation and global post-natal growth failure, variable mental retardation, facial anomalies including relative micrognathia and triangular facies and minor malformations of the extremities including proximally placed thumbs, cubitus valgus, and brachydactyly with tappering of the digits.     

Deletion of a common region on the long arm of chromosome 6 in acute lymphoblastic leukaemia

We have characterised a region of deletion on the long arm of chromosome 6 (6q) in six cases of acute lymphoblastic leukaemia, by fluorescence in situ hybridisation, using a series of YAC clones which map to 6q. Conventional cytogenetic analysis of four of these cases had been interpreted as showing terminal deletions of 6q. We demonstrated by FISH that in all cases the deletions were interstitial. D6S246 (6q16.3) was the only marker which was missing in all six cases, indicating a common region of deletion between the markers M6PI at 6q14–15 and FYN at 6q21. Our results suggest the presence of a tumour suppressor gene within this interval. Genes Chrom Cancer 10:26–29 (1994). © 1994 Wiley-Liss, Inc.     

Proportional growth failure and oculocutaneous albinism in a girl with a 6.87 Mb deletion of region 15q26.2-->qter

We report on an 8¹/₂-year-old girl with severe pre- and postnatal growth retardation, congenital heart malformation, facial asymmetry, oculocutaneous albinism without misrouting and subluxation of the radial heads. Her intelligence was in the low normal range. By GTG-banding a deletion of band 15q26 was found. Array-CGH, using a 3783 BAC array, revealed a segmental monosomy of the 15(q26.2→qter) region, which was narrowed down to a 6.87 Mb deletion by using the Illumina Infinium 317 K SNP array system, and subsequently confirmed by fluorescence in situ hybridisation (FISH) analysis. The deletion appeared to have arisen de novo. The IGF1R (insulin-like growth factor 1 receptor) and the NR2F2 genes were situated within, but the OCA2 (oculocutaneous albinism II) gene (formerly called the P gene) was located outside the deleted region. Clinical findings in our patient were compared with previously reported cases carrying terminal deletions of 15q26.2. This allowed us to expand the clinical phenotype of terminal 15q26.2 deletions and to indicate candidate genes for several phenotypic features.     

一个涉及1号和7号染色体插入易位家系的鉴定

目的 确定一个有反复流产史且常规G显带发现有7q末端缺失病例的核型,探讨染色体末端区域插入易位的形成机理。方法 应用显微切割制备的7号特异性全染色体探针和7q亚端粒（7q36→qter)探针,与病例的中期分裂相进行荧光原位杂交（fluorescence in situ hybridization,FISH)。结果 发现了该病例为常规G显带难以妈现的1号和7号染色体之间的插入易位,7q36→qter区域没有插入到1号染色体中,其异常核型来源于其母亲。结论 为染色体末端区域的插入易位仍然为一个三断裂重排。细胞遗传学上见到的末端缺失为中间缺失提供了实验证据,FISH与显微切割技术相结合。是检出染色体微小结构异常的一个强有力的工具。     

Proximal interstitial deletion of 7q: a case report and review of the literature

A male infant with multiple congenital anomalies was found to have a deletion of 7q [46,XY,del(7)(pter----q11.2::q22----qter)]. The father had a balanced rearrangement involving chromosomes 7 and 9, interpreted as 46,XY,dir ins(9;7), (9pter----9p12::7q22----7q11.2::9p12----++ +9qter;7pter---- 7q11.2::7q22----7qter). C-banding showed that the rearrangement occurred as a new event in the paternal grandfather's germ-line. Including the present patient, 16 cases of proximal 7q deletion (q11----q21/q22) have been described to date. This is a sufficient number of cases to permit comparison of manifestations to attempt delineation of karyotype-phenotype relationships in different proximal interstitial deletions of 7q.     

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.     

Patient with terminal duplication 3q and terminal deletion 5q: comparison with the 3q duplication syndrome and distal 5q deletion syndrome

Partial duplication of chromosome 3q is a well-described condition of multiple congenital anomalies and developmental delay that resembles the Brachmann-de Lange syndrome. Similarly, an emerging phenotype of a distal 5q deletion syndrome has recently been described. The combination of both chromosome abnormalities has not been previously described. We report on a child with both a de novo duplication of distal 3q (q27 --> qter) and terminal deletion of 5q (q35.2 --> qter). The patient had facial anomalies, hypoplastic toenails, lymphedema of the dorsum of the feet, type I Chiari malformation, a seizure disorder, and moderate developmental delays. The phenotype is compared and contrasted to the few reports of patients with similar terminal 3q duplications and 5q deletions. Our patient did not have the characteristic phenotype of the 3q duplication syndrome, suggesting that the chromosome region responsible for this phenotype is more proximal than the terminal 3q27 region. In addition, comparison with three other reported cases of terminal 5q35 deletions suggests a possible association of terminal 5q deletions with central nervous system (CNS) structural abnormalities.     

Retinoblastoma and long arm deletion of chromosome 13. Attempts to define the deleted segment

A girl with retinoblastoma, mild psychomotor retardation, bifid uvula and clinodactyly of the fifth fingers is described. A chromosome analysis revealed a long arm deletion of a D chromosome. An autoradiographic analysis, as well as G- and Q-banding analyses indicated a 13q- chromosome. Measurements of length, surface and relative reflection of the different light and dark bands in the normal and abnormal chromosome 13 pointed to an interstitial deIetion, mainly of band q21 (46, XX, de1(13) (pter→q14:: q22→qter) The chromosome findings and the clinical features of the patient are discussed and compared with other reported cases.     

Severe mental retardation - distal arthrogryposis in the upper limbs and complex chromosomal rearrangements resulting from a lOq25→qter deletion

Lukusa T, Devriendt K, Holvoet M, Fryns JP. Severe mental retardation - distal arthrogryposis in the upper limbs and complex chromosomal rearrangements resulting from a 10q25→qter deletion. CIin Genet 1998: 54: 224–230. 8 Munksgaard, 1998
We present the first report of chromosomal rearrangement involving chromosomes 4, 10 and 12. The proband was a 42–year-old woman with severe mental retardation and multiple congenital anomalies. The most striking physical anomalies were upper limb contractures resulting in distal arthrogryposis. As upper limb flexion contrdctures have been previously reported in individuals with partial distal 1Oq deletion, this sign should be considered as part of the clinical manifestations of 10q25→qter monosomy.     

Delineation of a critical region on chromosome 18 for the del(18)(q12.2q21.1) syndrome

Deletions involving the long arm of chromosome 18 have been reported in many patients. Most of these deletions are localized in the distal half of the long arm (18q21.1 --> qter) and are detectable by standard cytogenetic analysis. However, smaller interstitial deletions leading to a recognizable phenotype and residing in the region around chromosome band 18q12.3 (bands q12-q21) are less common. Here we report on an interstitial deletion of less than 1.8 Mb within chromosomal band 18q12.3. The phenotypic features of the propositus correspond well with those observed in patients with larger cytogenetically detectable deletions encompassing chromosome band 18q12.3. The deletion enabled us to define a critical region for the following features of the del(18)(q12.2q21.1) syndrome: hypotonia, expressive language delay, short stature, and behavioral problems.     

Interstitial deletion 4q32-34 with ulnar deficiency: 4q33 may be the critical region in 4q terminal deletion syndrome

We report on an infant with Robin sequence; mild developmental delay; a left ulnar ray defect with absent ulna and associated metacarpals, carpals and phalanges; and a right ulnar nerve hypoplasia. He had a de novo interstitial deletion of 4q32-->q34. The critical region involved in the 4q terminal deletion syndrome may be 4q33. This conclusion was suggested by showing that del(4)(q31qter), del(4)(q32qter), and del(4)(q33qter) result in a similarly severe phenotype. In addition, we propose that genes for distal arm development, in particular for development of the left ulnar ray, central nervous system development, and cleft lip and palate, may be located at 4q33.     

Chromosome 6q deletions: a report of two additional cases and a review of the literature

Here we report on two additional cases of distal 6q deletions with one case showing a terminal deletion of chromosome 6 (46,XY, del(6)(pter----q26:)) and one case showing an interstitial deletion of chromosome 6 (46,XY, del(6)(pter----q23::q25----qter)). The association of retinal abnormalities in 6q deletions is supported, and the additional manifestations of skin hyperextensibility, sacral abnormality, and imperforate anus are described.     

Is there a monosomy 10qter syndrome?

A case of terminal deletion 10q25→qter is reported. Comparison of the findings with those noted in the three previously published cases revealed marked clinical dissimilarities and some unusual features not hitherto described.     

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.