Ana I. Vásquez-Velásquez

A Girl with 15q Overgrowth Syndrome and dup(15)(q24q26.3) that Included Telomeric Sequences

Distal 15q trisomy or tetrasomy is associated with a characteristic phenotype that includes mild to moderate intellectual disability, abnormal behavior, speech impairment, overgrowth, hyperlaxity, long face, prominent nose, puffy cheeks, pointed chin, small ears, and hand anomalies (mainly arachno- and camptodactyly). We present the case of a 13-yr-old girl with the main clinical features of 15q overgrowth syndrome and a 46,XX,dup(15)(q24q26.3)[117]/46,XX[3].ish dup(15)(q24q26.3) (SNPRN+,PML+,subtel++,tel++) de novo karyotype. The findings in this case are consistent with those in the previous distal 15q trisomy cases that presented with overgrowth and mental retardation. Further, the rearranged chromosome had a double set of directly oriented telomeric and subtelomeric sequences.

Familial whole-arm translocations (1;19), (9;13), and (12;21): a review of 101 constitutional exchanges

We report here on 3 familial whole-arm translocations (WATs), namely the 8th instance of t(1;19)(p10;q10) and 2 novel exchanges: t(9;13)(p10;q10) and t(12;21)(p10;q10). The exchanges (1;19) and (12;21) were ascertained through a balanced carrier, whereas the t(9;13) was first diagnosed in a boy with a trisomy 9p syndrome and der(9p13p). Results of FISH analyses with the appropriate α-satellite probes were as follows. Family 1, t(1;19): the D1Z5 probe gave a strong signal on both the normal chromosome 1 and the der(1q19p) as well as a weak signal on the der(1p19q). Family 2, t(9;13): the centromere-9 alphoid and D13Z1/D21Z1 probes under standard stringency gave no signal on the der(9p13p) in both the proband and a carrier brother, whereas the der(9q13q) was labelled only with the centromere-9 alphoid repeat in the latter; yet, this probe under low stringency revealed a residual amount of alphoid DNA on the der(9p13p) in the carrier. Family 3, t(12;21): the D12Z3 probe gave a signal on the normal chromosome 12 and the der(12p21q), whereas the D13Z1/D21Z1 repeat labelled the der(12q21p), the normal chromosome 21, and both chromosomes 13. Out of 101 WATs compiled here, 73 are distinct exchanges, including 32 instances between chromosomes with common alphoid repeats. Moreover, 7/9 of recurrent WATs involved chromosomes from the same alphoid family. Thus constitutional WATs appear to recur more frequently than other reciprocal exchanges, often involve chromosomes with common alphoid repeats, and can mostly be accounted for the great homology in alphoid DNA that favours mispairing and illegitimate nonhomologous recombination.

5q35 duplication and Hunter–McAlpine syndrome: Missing the link†

TO THE EDITOR: In their recent report on a child with 5q34! q35 duplication, Kariminejad et al. [2009] refer to 39 comparable patients but omit at least 16 other reports concerning distal 5q duplications [Ad es et al., 1993; Nakayama et al., 1993; De Albuquerque Coêlho et al., 1996; Kriplani et al., 1998; Kotzot et al., 2000; Vogels et al., 2000; SanchezGarcia et al., 2001; Carbonell P erez et al., 2004; Bocian et al., 2005; Hunter et al., 2005; Koolen et al., 2006; Chen et al., 2006a,b; Kirchhoff et al., 2007; Buysse et al., 2008; Utine et al., 2008]. Of utmost relevance is the lackof any mention tothe close relationship or even samenessof this chromosomal entity with the syndrome first delineated in six affected members of a Canadian family and assumed to result from either an autosomal dominant allele or a chromosomal imbalance [Hunter et al., 1977]; in fact, it was recently shown that the patients in this family had a cryptic 5q35 duplication onto 13p and were connected through healthy carriers of a 5;13 translocation [Hunter et al., 2005]. Moreover, this finding led Hunter et al. [2005] to reassess by molecular methods a patient described with the eponym Hunter–McAlpine syndrome [Ad es et al., 1993], a quest that actually disclosed a similar 5q duplication onto 1q44. The inescapable conclusion that 5q35 duplication causes the Hunter–McAlpine syndrome was stressed by Chen et al. [2006b]. Thus, failing to cite these crucial articles appears to be the most sensible omission by Kariminejad et al. [2009] who otherwise would then have become aware of 7 out of 16 reports aforementioned. Since good papers are also characterized by appropriate literature reviews, it is hard to understand how some pertinent references are often overlooked even in articles published in prestigious journals [e.g., Rivera and Dom ınguez, 2007]; indeed, it is expected that the worldwide availability of valuable databases such as Medline would result in comprehensive bibliographies. Incidentally, a search in PubMed introducing ‘‘5q35 duplications’’ yields 15 references including both key papers: Chen et al. [2006b] and Hunter et al. [2005]. Although in principle an incomplete or otherwise faulty reference list is attributable to the authors, reviewers and editors are also co-responsible as their main duty is precisely to ensure the quality and integrity of any published article. Lastly, these remarks recall the dictum that real peer review starts only after publication [Adam and Knight, 2002]. REFERENCES

Concurrent psu dic(21)(q22.3) and t(13;17)(q14.1;p12) in a mosaic Down's syndrome patient: review of thirty-one similar dicentrics.

Pseudodicentric ‘mirror-image’chromosomes 21 with breakage and reunion at 21q22 and satellites on both ends have been ascertained in 46 chromosome Down’s syndrome (DS) patients since the prebanding era (e.g., Richards et al. 1965). A distal deletion was first suspected on banded chromosomes (Cantú et al. 1980) and then confirmed by molecular methods in several cases (Pangalos et al. 1992; Wandall et al. 2002; Sheth et al. 2007; Egashira et al. 2008). Here we report on the concurrence in a DS infant of a psu dic(21)(q22) with a balanced t(13;17)(q14.1;p12) and summarize 30 unequivocally identified psu dic(21)(q22) chromosomes found in sporadic DS patients (Jernigan et al. 1974; López-Pajares et al. 1976; Kosztolanyi 1988; Pangalos et al. 1992; Sánchez et al. 2001; Sheth et al. 2007; Sato et al. 2008; Thi et al. 2010, and references therein); further three instances alluded only in abstracts were disregarded because no parental data were given.

Apparent Neotelomere in a 46,X,del(X)(qter→p11.2:)/46,X,rea(X)(qter→p11.2::q21.2→qter) Novel Mosaicism: Review of 34 Females with a Recombinant-Like dup(Xq) Chromosome

A 26-year-old woman with secondary amenorrhea and turneroid stigmata was found to have a 46,X,rea(X)(qter→p11.2::q21.2→qter)/46,X,del(X)(qter→p11.2:) mosaicism in 101 G-banded metaphases (71 and 30, respectively). The mothers karyotype was normal (the father was already deceased). A fully skewed inactivation of both abnormal X-chromosomes was documented in RBG-banded metaphases and by means of the HUMARA assay. In addition, the latter revealed that the involved X-chromosome was the paternal one. The patients secondary amenorrhea and turneroid stigmata can reliably be ascribed to her nearly complete Xp deletion present in all cells. Thus, this observation is consistent with the well-known gradation of ovarian function depending on the Xp deletion size. We assume that the first event was an intrachromosome recombination during paternal meiosis between paralogous sequences at Xp11.2 and Xq21.2, which resulted in a fertilizing rea(X) spermatozoid. Early in embryogenesis, the rea(X) dissociated at the Xp11.2 junction point to originate the del(X), which in turn was healed by the de novo addition of telomeric repeats (the acentric Xq21.2→qter segment was lost in the process). The reverse sequence appears unlikely because it implies that the del(X) chromosome was healed only after it undergone a postzygotic interchromatid recombination and apposite segregation required to obtain the rea(X) clone. The present observation further expands the cytogenetic heterogeneity in Turner syndrome and may represent another instance of a terminal deletion healed by the de novo addition of telomeric repeats.

A 9p13→p24 duplication coupled with a whole 22q translocation onto 9p24

We report on a 3-year-old girl with a typical 9p trisomy syndrome, whose 45-chromosome karyotype includes a 9p+. As assessed by G, C and Ag-NOR bands, the rearranged chromosome resulted from a 9p13 → p24 direct duplication coupled with a translocation of the whole 22q onto 9pter, had heterochromatin at the junction site, lacked both nucleolar organizing regions (NORs) and centromere dots at the unconstricted fusion point, and was present in all metaphases scored. FISH results: a 9p subtelomere probe gave a diminished signal on the 9p+ precisely at the duplication junction 9p24∷9p13, but no labeling was observed at the 9;22 translocation site; a pancentromeric alphoid probe labeled all centromeres, and gave a distinct signal at the 9pter;22cen junction. Hence, her karyotype was 45,XX,rea(9;22)(9qter→9p24::9p13→9p24::22p10→22qter).ishrea(9;22)(9psubtel+ dim,pancen+). Parental chromosomes were normal. The distinctiveness of the present centromere-telomere fusion rests on the coupling of an intrachromosomal distal duplication with a whole-arm translocation including alphoid DNA onto the duplicated segment. The centromeric inertia of the residual alphoid DNA in the present case compares with the variable functional status of the chromosome 22 centromere in true heterodicentrics involving such a chromosome.

Two further triple-X/rea(X) females in an inv(X)(p22q22) family.

Recently two reports published in this journal described the exceptional concurrence of triple-X aneuploidy with a rearranged X chromosome, namely a maternal Xq+ transmitted to two 47,XX,add(X)(q26) sisters (Ramachandram et al. 2013) and a de novo Xp deletion in a 47,XX,del(X)(p21) patient (Malla et al. 2014). In addition, two sporadic and unrelated 45,X/46,X,rea(X)/47,X,rea(X),rea(X) females are also known (Daly et al. 1977; Reinehr et al. 2001). These observations prompt us to describe here a comparable concurrence in a family with an inv(X)(p22q22) that was first diagnosed in a 14-year-old girl with a height of 135 cm (<3rd centile) and delayed milestones. The inverted X was inherited from her 46-chromosome mother but the same condition was also found in her sister and maternal grandmother who were triple-X females and had an unremarkable clinical phenotype.

In-house plagiarism and editorial unaccountability.

A BCritical Perspectives^ article in the Journal of Bioethical Inquiry on scientific integrity in Brazil summarizes several misconduct cases documented therein (Lins and Carvalho 2014). To further reinforce the responsible conduct of research in developing countries and to fight against the unaccountability of many editors (Smith 2008; Balhara 2011), we describe here a Mexican instance of alleged in-house plagiarism (Resnik 2013). In June 2011, we submitted a BCorrespondence^ note to a Nature group journal to expose what we claimed to be a breach of collegiality and inappropriate authorship in a three-page mutation report just published in that journal. Our main complaints were two: (1) the surreptitious way in which we believed that both displayed metaphases in that report had been obtained from our files by a local colleague and then published without our consent and (2) the massive easy-on co-authorship: 14 out of 21 co-authors declared just to have Bprovided clinical material.^ In contrast, the contributions of the first, the corresponding, and five other co-authors are in line with the authorship requirements of Nature journals (Editorial 2009). One month later, the journal wrote to us that it had Basked the authors of the cited paper for a response to your criticisms^ and rejected our complaint. Ironically, the expected outcome of an allegation of plagiarism among collaborators made to institutional officials often is plain dismissal as an authorship dispute (Resnik 2013), even if such allegations go beyond authorship issues (Scott-Lichter 2012). In this regard, several authors (Anderson et al. 2007; Sovacool 2008) have remarked on the increased assimilation of modern science to market capitalism and the concomitant derived perverse effects, including the deformation of relationships among peers and the risk to do careless or questionable research. We believe that the editorial procedure adopted in this case of seeking a reply from the concerned authors (in spite of the manifest conflict of interest) has violated the confidentiality owed to all submitted manuscripts (Godlee 2004); i.e., even if this is a contentious matter, it is clear to us that any correspondence or letter to the editor with critical remarks should be forwarded to the concerned authors only after it has been accepted and thereby to offer them the opportunity to reply (Rivera 2009). As for the author’s exclusive right to disclosure, article 9(1) of the Berne Convention (1979) states: BAuthors of literary and artistic works protected by this Convention shall have the exclusive right of authorizing Bioethical Inquiry (2015) 12:21–23 DOI 10.1007/s11673-015-9620-1