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Overview of the chromosomal abnormalities in all the reported pure 3q duplication syndrome cases found. A critical region of 3q duplication at the chromosomal 3q26.31-q27.3 region is essential for the characteristic clinical phenotype.
Source publication
We report here a very rare case of de novo inversion-duplication chromosomal abnormality with a pure 3qter duplication syndrome. Interestingly, the 3q duplication includes an overlap of the syndrome's critical region. Although there have only been 9 cases of this syndrome reported in the past, our patient had more severe neurological abnormalities...
Context in source publication
Context 1
... report is a very valuable source of information for the clinical syndrome resulting from pure 3q duplication, given the scarcity of such cases. Furthermore, the etiology of many of the reported 3q duplication syndromes is duplication of 3q21→qter, and to the best of our knowledge only 9 individuals with pure 3q duplication syndrome have been reported in the literature (2-9). Our case represents the 10th case; Fig. 3 for a graphic comparison of the partial 3q trisomy in our case with the others available. In pure 3q duplication syndrome, it is not necessary to consider the monosomy of another chromosomal fragment when analyzing the etiology of phenotypic clinical features. Thus, careful comparison of the clinical features described in other pure 3q duplications can help elucidate the influence of specific gene critical regions on the phenotype. Faas et al reported a de novo 3q duplication syndrome with descriptions of 6 other previous cases and concluded that a critical region responsible for the 3q duplication phenotype could be assigned to 3q26.31-q27.3 (7). In this study, our case was analyzed in view of the previous reports; our 3q partial trisomy overlaps with the described critical region on chromo- some 3. Moreover, the severity of the motor and intellectual deficiencies in our case is uncommon. This may be due to the specific chromosomal fragments involved in the inversion- duplication in our case when compared to the syndromes described in past reported cases (2)(3)(4)(5)(6)(7)(8). More cases should be examined in the future in order to fully understand the charac- teristics of pure 3q duplication ...
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Citations
... In 1966, Falek et al. [4] described the first subject affected with partial duplication 3q, and since then around 100 patients have been reported [5]. The critical region associated with the syndrome phenotype was later mapped to 3q26.3q27.7 [6,7]. Cases with pure and more distal duplications have been rarely reported, and even more uncommon are those identified through prenatal diagnostic tests [8]. ...
Background:
Duplications of the long arm of chromosome 3 are rare, and associated to a well-defined contiguous gene syndrome known as partial trisomy 3q syndrome. It has been first described in 1966 by Falek et al., and since then around 100 patients have been reported. Clinical manifestations include characteristic facial dysmorphic features, microcephaly, hirsutism, congenital heart disease, genitourinary anomalies, hand and feet abnormalities, growth disturbances and intellectual disability. Most of cases are due to unbalanced translocations, inherited from a parent carrying a balanced aberration (reciprocal translocation or inversion), and rarely the genomic anomaly arises de novo. Very few studies report on the prenatal identification of such rearrangements.
Case presentation:
Hereby, we report on a newborn with a rare pure duplication of the long arm of chromosome 3. Noninvasive prenatal test (cell free fetal DNA analysis on maternal blood), performed for advanced parental age and use of assisted reproductive technique, evidenced a partial 3q trisomy. Then, invasive cytogenetic (standard and molecular) investigations, carried out through amniocentesis, confirmed and defined a 3q27.1-q29 duplication spanning 10.9 Mb, and including about 80 genes. Our patient showed clinical findings (typical facial dysmorphic features, esotropia, short neck, atrial septal defect, hepatomegaly, mild motor delay) compatible with partial trisomy 3q syndrome diagnosis, in addition to pre- and postnatal overgrowth.
Conclusions:
Advanced parental age increases the probability of chromosomal and/or genomic anomalies, while ART that of epigenomic defects. Both conditions, thus, deserve more careful prenatal monitoring and screening/diagnostic investigations. Among the latter, cell free fetal DNA testing can detect large segmental aneuploidies, along with chromosomal abnormalities. It identified in our patient a wide 3q rearrangement, then confirmed and defined through invasive molecular cytogenetic analysis. Neonatologists and pediatricians must be aware of the potential risks associated to duplication syndromes. Therefore, they should offer to affected subjects an adequate management and early and careful follow-up. These may be able to guarantee to patients satisfactory growth and development profiles, prevent and/or limit neurodevelopmental disorders, and timely recognition of complications.
... These imbalances were later traced to a balanced reciprocal translocation in the father (Fig. 2B), establishing the karyotype for the foetus as 46,XY,der(5) t(3;5)(q26.2;p13)pat. The 3q duplication [dup(3q)] syndrome is rare, usually diagnosed after birth [47,48], and is characterised by anomalies in the limbs and possible association with internal malformations, growth deficiency, dysmorphic face, and cognitive deficits [49]. Pasińska et al. [50] reported a prenatal diagnosis of 3q duplication syndrome in a foetus with enlarged skin oedema up to the sacral and pericranial regions with a NT of 8 mm. ...
Background
Since 2011, screening maternal blood for cell-free foetal DNA (cffDNA) fragments has offered a robust clinical tool to classify pregnancy as low or high-risk for Down, Edwards, and Patau syndromes. With recent advances in molecular biology and improvements in data analysis algorithms, the screening’s scope of analysis continues to expand. Indeed, screening now encompassess additional conditions, including aneuploidies for sex chromosomes, microdeletions and microduplications, rare autosomal trisomies, and, more recently, segmental deletions and duplications called copy number variations (CNVs). Yet, the ability to detect CNVs creates a new challenge for cffDNA analysis in couples in which one member carries a structural rearrangement such as a translocation or inversion.
Case presentation
We report a segmental duplication of the long arm of chromosome 3 and a segmental deletion of the short arm of chromosome 5 detected by cffDNA analysis in a 25-year-old pregnant woman. The blood sample was sequenced on a NextSeq 550 (Illumina) using the VeriSeq NIPT Solution v1 assay. G-band karyotyping in amniotic fluid only detected an abnormality in chromosome 5. Next-generation sequencing in amniocytes confirmed both abnormalities and identified breakpoints in 3q26.32q29 and 5p13.3p15. The foetus died at 21 weeks of gestation due to multiple abnormalities, and later G-band karyotyping in the parents revealed that the father was a carrier of a balanced reciprocal translocation [46,XY,t(3;5)(q26.2;p13)]. Maternal karyotype appeared normal.
Conclusion
This case provides evidence that extended cffDNA can detect, in addition to aneuploidies for whole chromosomes, large segmental aneuploidies. In some cases, this may indicate the presence of chromosomal rearrangements in a parent. Such abnormalities are outside the scope of standard cffDNA analysis targeting chromosomes 13, 18, 21, X, and Y, potentially leading to undiagnosed congenital conditions.
... [4,6,7]. It is a rare genetic syndrome in which many defects are observed, usually diagnosed after birth [7,8]. The critical region responsible for the typical phenotype of the dup(3q) syndrome has been mapped at the regions 3q26.3-q27.7 [9,10]. ...
... The phenotypic discrepancy between the patients can be explained by variations of the number of active genes present in chromosomal fragments of different sizes [3,9,11]. Numerous developmental defects are the cause of short survival, and according to data from the literature, almost 40% of children with this syndrome die during the first year of life [5,8,11]. ...
... Pure duplications of 3q are rare because most of the reported patients are found to carry unbalanced translocations [6,8]. ...
Background:
The 3q duplication syndrome is a result of duplication of a large fragment of the long arm of chromosome 3, mainly 3q21-qter, and in most cases it is diagnosed only after birth. The phenotypic consequences resulting from genetic imbalance are an important source of information for genetic counselling, especially in prenatal diagnostics. However, in most cases it is impossible to define them precisely because the final clinical presentation is a result of an overlap, usually due to different sizes of deletions and/or duplications not only chromosome 3 but also of translocation partner chromosome. In this article, we present a prenatal diagnosis of the 3q duplication syndrome in a foetus, arising from a balanced insertion ins (7,3)(q21.2;q12.3q29) carried by the mother.
Case presentation:
The article presents a case of a 29-year-old woman referred to the Genetic Outpatient Clinic for consultation in the 12th week of her fifth pregnancy with a diagnosis of generalised hydrops foetalis. The analysis of karyotype using GTG technique and FISH allowed diagnosis of a balanced aberration in the mother, and determined the type of chromosomal rearrangement, which allowed the identification of the origin of the additional genetic material in the foetus and the previous malformed child of the same couple. The use of molecular karyotyping techniques (FISH and aCGH) allowed a precise determination of the size of the imbalanced fragments in the affected siblings.
Conclusions:
The aCGH technique is particularly valuable for the diagnostics of submicroscopic deletions and duplications, if no imbalanced chromosomal aberrations are detected by routine cytogenetic tests. It is also a valuable technique for identifying and fully characterizing genetic material of unknown origin, which can't be identified using routine cytogenetic techniqes. However, it does not allow identification of balanced aberrations in carriers.
... Our case is the 13 th one and has novel findings concerning eye involvement. 3,7 . In our patient anterior and posterior segment dysgenesis, thin sclera and iris dysgenesis were detected besides the previously identified features ( Table I). ...
Kahvecioğlu D, Tatar-Aksoy H, Yıldız E, Bakır A, Alioğlu B. A rare chromosomal disorder in a newborn: Trisomy 3q. Turk J Pediatr 2019; 61: 271-274. Trisomy 3q is a rare chromosomal disorder that leads to multiple congenital abnormalities. We hereby present a patient with chromosomal karyotype 46, XY, dup (3)(q23-29), which can be classified as pure 3q duplication and has thin sclera and iris dysgenesis, anterior and posterior segment dysgenesis besides the previously identified specific facial features. To the best of our knowledge only 12 cases have been reported with pure duplication in the literature. Our case is the 13th one reported and has noval findings concerning eye involvement. The ocular manifestations of the 3q duplication syndrome provide additional evidence of the involvement of genes which are responsible for eye development in this chromosomal region.
