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We describe the clinical and cytogenetic findings in a boy with an unbalanced karyotype involving monosomy for 3q27-q29. He does not resemble other reported cases of del(3q). Deletions of the long arm of chromosome 3 are extremely rare, having been reported in five cases, only two of which had terminal 3q deletions.
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Background & objectives: Subtelomeres are prone to deleterious rearrangements owing to their proximity to unique sequences on the one end and telomeric repetitive sequences, which increase their tendency to recombine, on the other end. These subtelomeric rearrangements resulting in segmental aneusomy are reported to contribute to the aetiology of i...
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... Her mother has normal intelligence and no dysmorphic features. We searched the literature using PubMed and MedLine and found 4 individuals with 3q chromosomal deletions detected by karyotype which may involve LPP [Brueton et al., 1989;Chitayat et al., 1996;Davies and Mathew 1997;Jokiaho et al., 1989]; 13 patients with deletions detected by microarray and ascertained for autism which includes LPP within the 5 breakpoints [Gai et al., 2012;Kaminsky et al., 2011;Kousoulidou et al., 2013;Lesca et al., 2012;Sanders et al., 2011]; and one patient with a deletion detected by microarray and ascertained for a cardiac lesion which includes LPP within the breakpoints [Tomita-Mitchell et al., 2012]. One of the four karyotype-ascertained patients had a persistent ductus arteriosus and none of the 13 autism microarray patients had clinical details included. ...
... Case reports involving an interstitial or a terminal deletion of 3q26.33 and/or 3q27 have rarely been reported (Alvarez Arratia et al., 1984; Sargent et al., 1985; Brueton et al., 1989; Jokiaho et al., 1989; Chitayat et al., 1996; Male et al., 2002; Senzaki et al., 2003; Guichet et al., 2004; Pollazzon et al., 2009; Mandrile et al., 2013; Salem et al., 2013; Zarate et al., 2013; Castori et al., 2014; Dasouki et al., 2014; Thevenon et al., 2014). The involvement of SOX2 (OMIM*184429) within the deleted 3q-area of such patients seems to predispose toward an ophthalmic phenotype (Male et al., 2002; Guichet et al., 2004; Salem et al., 2013). ...
Chromosomal abnormalities involving an interstitial or a terminal deletion of 3q26.33 and/or 3q27 have rarely been described. Here we report on a fetus of 22+1 weeks' gestational age with severe intrauterine growth restriction and multiple abnormalities detected by ultrasound examination. Post-mortem molecular cytogenetic investigation (array-comparative genomic hybridization) identified a de-novo interstitial ∼6.17 Mbp microdeletion of 3q26.33q27.3. The clinical and molecular findings in this patient are compared with the previous literature on cases with overlapping interstitial 3q-deletions (seven cases in total). The common phenotype observed in patients with a microdeletion involving 3q26.33q27.3 includes severe prenatal and postnatal growth retardation (including microcephaly), developmental delay, central nervous system anomalies, and several facial characteristics (abnormally shaped ears, broad nasal tip, epicanthal folds, micrognathia/retrognathia, short philtrum). No genotype-phenotype correlation could be established for severe (intrauterine) growth retardation. We conclude that deletions of 3q26.33q27.3 are associated with a profoundly abnormal phenotype, with severe intrauterine growth retardation as its most striking feature.
... Most of the inversions are not clearly visualized by GTG banding [Hasle et al., 1992] and therefore not frequently reported [Welborn, 2004]. Nevertheless a few cases of chromosome 3 abnormalities associated with SS were reported in literature [Barajas-Barajas et al., 2001], like a 3q deletion with SS reported by Nguyen [Nguyen et al., 2005] and a partial monosomy 3q with SS reported by Brueton et al., 1989. Most of other cases were associated with other chromosomal rearrangements [Kondo et al., 2006;Stine et al., 1982;Yip et al., 1996]. ...
... In addition to the 22 cases of interstitial 3q deletions that Ramieri et al. (2011) cited, there are at least four more cases with deletions limited to 3q13.1-q13.33 (Lawson-Yuen et al., 2006;Shimojima et al., 2009;Simovich et al., 2008), and 19 more cases involving at least part of 3q21-q23 (with some extending to 3q13) (Almenrader et al., 2008;Arai et al., 1982;Brueton et al., 1989;Callier et al., 2009;Croft and Turnpenny, 2008;De Baere et al., 2001, 2005Engelen et al., 2002;Genuardi et al., 1994;Jenkins et al., 1985;Mackie Ogilvie et al., 1998;McMorrow et al., 1986;Okada et al., 1987;Sargent et al., 1985;Tohyama et al., 2010;Willemsen et al., 2010;Zahanova et al., 2012;Zhou et al., 2010), with a few more microdeletions associated with apparently balanced translocations. In a cohort of BPES patients whose deletions were mapped by BAC clones, there are also four cases (two microscopic and two submicroscopic) with deletions including FOXL2 and additional genes (Beysen et al., 2009), and another 12 BPES patients with deletions of at least 2.48 Mb (D'Haene et al., 2010). ...
We describe a boy with a de novo deletion of 15.67 Mb spanning 3q22.1q24. He has bilateral micropthalmia, ptosis, cleft palate, global developmental delay and brain, skeletal and cardiac abnormalities. In addition, he has bilateral inguinal hernia and his right kidney is absent. We compare his phenotype with seven other patients with overlapping and molecularly defined interstitial 3q deletions. This patient has some phenotypic features that are not shared by the other patients. More cases with smaller deletions defined by high resolution aCGH will enable better genotype-phenotype correlations and prioritizing of candidate genes for the identification of pathways and disease mechanisms.
... Large cytogenetically visible terminal deletions of chromosome 3 (3q27-ter) had been previously reported [Alvarez et al., 1984;Sargent et al., 1985;Brueton et al., 1989;Jokiaho et al., 1989;Chitayat et al., 1996;Senzaki et al., 2003;Pollazzon et al., 2009;Wang et al., 2010] in nine patients four of whom died in early childhood. As a group, they had significant structural abnormalities including cleft lip and palate, cerebral atrophy, Dandy-Walker malformation, meningocele and cardiomyopathy. ...
The human 3q29 microdeletion syndrome is associated with mild facial dysmorphism, developmental delay and variable congenital malformations. We report three new unrelated patients with this syndrome. We also performed in silico RNA binding analysis in silico on the 3q29 critical region genes. Several genes within this genomic region including DLG1 and RNF168 are predicted to bind RNA. While recessive mutations in RNF168 cause RIDDLE syndrome, an immune deficiency and radiosensitivity disorder, the potential impact of heterozygous deletion of RNF168 on patients with the 3q29 deletion syndrome is still unknown.
... Our patient 1 was thought to have a terminal deletion of 3q on initial chromosome analysis, but proved to have an interstitial deletion. If the cases reported by Jokiaho et al., 16 Sargent et al. 14 and Brueton et al. 15 were true terminal deletions of 3q, the deleted chromosomal regions may not overlap at all. Alternatively, the affected patients may already have a mutation in the gene on the non-deleted chromosome, which is 'unmasked' by the loss of the second copy by chromosomal deletion. ...
Anophthalmia or microphthalmia occur in approximately one in 10 children who have severe visual impairment. These eye malformations are often of unknown aetiology, but can be inherited in autosomal dominant, recessive or X-linked forms, and can also occur in association with specific chromosome abnormalities. Four children are described in the medical literature with microphthalmia or anophthalmia in association with chromosome rearrangements involving distal 3q, suggesting the presence of a micro/anophthalmia gene in this region. We have identified two further patients with micro/anophthalmia and chromosome rearrangements involving 3q26-->3q27 and identified a 6.7 MB common deleted region. Patient 1 had multiple abnormalities including bilateral anophthalmia, abnormalities of the first and second cranial nerves and partial absence of the corpus callosum. His karyotype was 46,XY,del(3)(q26.33q28). Patient 2 had right anophthalmia and left extreme microphthalmia. Her karyotype was 46,XX,del(3)(q26.33q28)t(3;7)(q28;q21.1). Both patients had intrauterine growth retardation (IUGR) and strikingly similar dysmorphic facies consisting of bossed forehead, downward-slanting palpebral fissures, grooved bridge of the nose, prominent low-set ears, small down-turned mouth and small mandible. We identified BAC clones mapping to distal 3q from the ENSEMBL and NCBI Entrez databases. These BAC clones were used as fluorescence in situ hybridisation (FISH) probes to identify the minimum deleted region common to both patients. This interval, between clones RPC11-134F2 and RPC11-132N15, was estimated to be 6.7 MB. We conclude that there is an anophthalmia locus within this interval. Candidate genes mapping to this region include Chordin and DVL3, a homologue of the Drosophila Dishevelled gene.
... However, the reciprocal unbalanced karyotype with terminal deletion 3q and terminal duplication 16p was not detected in our family. Although there are several reports of liveborn patients with partial 16p duplication (Léonard et al. 1992;O'Connor and Higgins 1992) and four reports of live-born patients with partial 3q deletion (Alvarez Arratia et al. 1984;Sargent et al. 1985;Brueton et al. 1989;Jokiaho et al. 1989), we propose that an unbalanced karyotype with a combination of both chromosome abnormalities is somehow selected against. Since there is no history of an increased rate of spontaneous abortion in this family, there might be prezygotic selection against gametes carrying such unbalanced chromosomal complements. ...
In the search for genetic causes of mental retardation, we have studied a five-generation family that includes 10 individuals in generations IV and V who are affected with mild-to-moderate mental retardation and mild, nonspecific dysmorphic features. The disease is inherited in a seemingly autosomal dominant fashion with reduced penetrance. The pedigree is unusual because of (1) its size and (2) the fact that individuals with the disease appear only in the last two generations, which is suggestive of anticipation. Standard clinical and laboratory screening protocols and extended cytogenetic analysis, including the use of high-resolution karyotyping and multiplex FISH (M-FISH), could not reveal the cause of the mental retardation. Therefore, a whole-genome scan was performed, by linkage analysis, with microsatellite markers. The phenotype was linked to chromosome 16p13.3, and, unexpectedly, a deletion of a part of 16pter was demonstrated in patients, similar to the deletion observed in patients with ATR-16 syndrome. Subsequent FISH analysis demonstrated that patients inherited a duplication of terminal 3q in addition to the deletion of 16p. FISH analysis of obligate carriers revealed that a balanced translocation between the terminal parts of 16p and 3q segregated in this family. This case reinforces the role of cryptic (cytogenetically invisible) subtelomeric translocations in mental retardation, which is estimated by others to be implicated in 5%–10% of cases.
Individuals with terminal deletion of the long arm of chromosome 3 are rare and survival into adulthood has not been previously reported. A 15-year-old with this condition was studied and the difficulties in management of the manifest behaviours are described. This chromosomal abnormality may be associated with mental and functional deterioration as well as severe self-injurious behaviour, commencing in early childhood.
It has been suggested that pericentric inversions of chromosome 2 increase the risk for spontaneous abortion but do not increase the risk for unbalanced recombinant offspring. We report our experience of a familial pericentric inversion of chromosome 2 resulting in two unbalanced recombinant offspring. Both subjects have 46,XX,rec(2),dup q,inv(2)(p25q35).
This is a case report of a 16-year-old Arab girl with mental subnormality, shortness of stature and multiple minor phenotypic anomalies. She is obese with normal secondary sexual characteristics, and has a speech deficit. Cytogenetic studies showed a 46,XX,dir ins (18;3)(p11.1;q13.2-->q25). The chromosome arrangement appeared balanced. Her condition is not a recognizable specific syndrome; thus, it remained unclear as to whether her condition is attributable to disruption of 3q or 18p or both. Further cytogenetic analysis by molecular biologists is required to solve this problem.
