Neocentromeres are fully functional centromeres that have arisen in previously noncentromeric chromosomal locations on rearranged chromosomes. The formation of neocentromeres results in the mitotic stability of chromosomal fragments that do not contain endogenous centromeres and that would normally be lost. Here we describe a unique collection of eight independent patient-derived cell lines, each of which contains a neocentromere on a supernumerary inversion duplication of a portion of human chromosome 13q. Findings in these patients reveal insight into the clinical manifestations associated with polysomy for portions of chromosome 13q. The results of FISH and immunofluorescent analysis of the neocentromeres in these chromosomes confirm the lack of alpha-satellite DNA and the presence of CENtromere proteins (CENP)-C, -E, and hMAD2. The positions of the inversion breakpoints in these chromosomes have been placed onto the physical map of chromosome 13, by means of FISH mapping with cosmid probes. These cell lines define, within chromosome 13q, at least three distinct locations where neocentromeres have formed, with five independent neocentromeres in band 13q32, two in band 13q21, and one in band 13q31. The results of examination of the set of 40 neocentromere-containing chromosomes that have thus far been described, including the 8 neocentromere-containing chromosomes from chromosome 13q that are described in the present study, suggest that chromosome 13q has an increased propensity for neocentromere formation, relative to some other human chromosomes. These neocentromeres will provide the means for testing hypotheses about sequence requirements for human centromere formation.

Mosaic variegated aneuploidy (MVA) is a rare autosomal recessive syndrome related to BUB1B gene mutations and characterized by multiple mosaic aneuploidies, cancer predisposition, and a distinct phenotype. We report on two mildly affected sibs with MVA syndrome but without BUB1B mutation. Both patients exhibited growth retardation, frontal bossing, triangular face and micrognathia but not microcephaly or cancer. Aneuploidies were assessed both in G-banded metaphases from lymphocyte cultures and in interphase nuclei from buccal cells by FISH. Screening of 23 exons and intron-exon boundaries of BUB1B was also carried out. These patients were then compared with other 19 MVA patients screened for BUB1B mutations. Around one half of the cultured lymphocytes from our patients had aneuploidies ranging from nullisomies to heptasomies; the most frequent abnormalities were trisomies (42%) and monosomies (28%). FISH results demonstrated more chromosomal losses than gains. Screening of BUB1B in our two patients failed to identify any mutation. A review of the 21/35 patients screened for BUB1B demonstrated three clinical pictures. Patients with monoallelic BUB1B mutations were severely affected with Dandy-Walker complex (7/8), cataracts (6/6), and Wilms' tumor (7/8); premature chromatid separation (PCS) was observed in 8/8 propositi and 7/7 carrier parents. Patients without BUB1B mutations were mildly affected with no evidence of cancer, Dandy-Walker malformation or cataract, and rarely (1/7) showed PCS. Finally, patients with biallelic BUB1B mutations showed a moderate phenotype. The distinct MVA clinical groups delineated here point to involvement of at least another mitotic spindle checkpoint gene in addition to the BUB1B gene.

The chromosomal origins and in some cases the molecular composition of 26 autosomal supernumerary marker chromosomes (SMC) were identified using combined fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) techniques. Fifteen were de novo, 4 maternally and 2 paternally transmitted and in 5 cases the parental origin is not known. Eleven cases were non-mosaic and fifteen cases had SMC cell lines ranging from 8-87%. Ten cases were ascertained prenatally, nine postnatally with abnormal phenotypes, three with poor reproductive histories and four co-incidentally. Five SMC were small rings from chromosomes 3, 6 (2 cases), 20 and 21; 8 were bisatellited from chromosomes 13/21 (4 cases), 14 (3 cases) and 14/22 (1 case). The remaining 13 appeared to be minutes comprising centromeric material only from chromosomes 1, 4, 12, 13/21 (2 cases), 14 (3 cases), 16 (2 cases), 19; 5/19, and a centric fusion involving 13 or 21 and 14. Euchromatin was detected in 9 out of 18 SMC tested with paints and/or PCR, and abnormal phenotypes were most commonly observed in patients with small ring shaped SMCs containing euchromatic sequences. Uniparental paternal isodisomy (UPD) for chromosome 6 was detected in one patient but was the only example of UPD for the normal homologues in association with an autosomal SMC in an overall total of 30 cases examined.

A family with a distinct form of congenital generalized hypertrichosis was studied. Males were more severely affected than females, who exhibited asymmetric hair distribution. This finding was attributed to lyonization, since genealogical studies indicated an X-linked pattern of inheritance. A back mutation is postulated as the origin of this new phenotype.

A maternally transmitted Xp + chromosome was associated with an abnormal

We analyzed 33 cases of Prader-Willi syndrome (PWS) (including 2 personal observations) with translocations of 15q1----qter onto the terminals of different, apparently whole chromosomes. In all but one of the 23 informative cases the translocations was de novo. Thirty of the patients were unbalanced and 27 had a 45-chromosome constitution compatible with a 3:1 segregation. One balanced and 2 unbalanced translocations were jumping ones. The possible existence of actual non-reciprocal translocations in man is indicated by the following considerations about these and other PWS-associated rearrangements: 1) The observed excess of de novo translocations; 2) the relatively frequent familial occurrence of reciprocal 15q translocations; 3) the concurrence in 3 terminal translocation cases of an idic (15); 4) the visualization of jumping terminal translocations as simple transpositions rather than as successive reciprocal exchanges; 5) the predominance of true isodicentrics in PWS patients with extra inv dup(15) chromosomes; and 6) the rarity of extra derivatives resulting in 15q proximal tertiary trisomy. Additional findings in the present series were normal parental age in the de novo 45-chromosome cases, an apparently random distribution of telomeric breakpoints, and the occurrence of different breakpoints within the 15q1 region.

A case involving a 6-year-old boy with Peutz-Jeghers syndrome and an unilateral feminizing Sertoli cell tumor is described. Endocrinologic studies revealed consistently high plasma and urine levels of estrogens and normal levels of testosterone and dihydrotestosterone. The increased levels of estrogens did not show changes that could be correlated with exogenous gonadotropin administration, thus indicating an autonomous nature. The histopathologic studies of nontumorous testicular tissue revealed changes in the seminiferous tubules which suggested that estrogens, directly or indirectly, may have had both stimulating and atrophying effects. It is concluded that gonadal tumors are an additional manifestation of the Peutz-Jeghers syndrome gene in both male and female patients.Cancer 46:223-228, 1980. whose propensity for malignancy is still uncertain.6Jfi~17~z0~2Y Ovarian tumors are more common in women with Peutz-Jeghers syndrome than in the general female p~p u l a t i o n ;~~~*~~~~~ however, no association between Peutz-Jeghers syndrome and gonadal tumors has been reported in the male patient. The purpose of this report is to describe for the first time, the association of Peutz-Jeghers syndrome with a Sertoli cell tumor, to emphasize the variable expressivity and pleiotropism of the causal gene, and to correlate the testicular histopathologic findings with the tumoral endocrine dysfunction. Accepted for publication July 6, 1979. Case Report Clinical and Familial DataThe 6-year-old patient was the second child of nonconsanguineous parents; aged 27 (father) and 28 (mother) years at his birth. The pregnancy, delivery, and psychomotor development were normal. An urethral meatotomy was performed when he was four years old because of congenital stenosis. At five years of age, medical consultation was sought for bilateral gynecomastia with an evolution of about two years; it was progressive, painless, without galactorrea, with slight predominance on the right side and associated with a rapid increase in stature. He also had numerous small (1-4mm) blackish macules on the lips and the buccal mucous membranes, without any additional symptoms. Upon physical examination at five years; seven months of age, the following somatometric data were found: height, 119 cm (above the 97th percentile corresponding to about the 50th percentile for seven and a half years); weight, 24 kg; arm span, 119 cm; upper to lower segment ratio, 1.05; and cephalic, thoracic and abdominal circumferences of 5 2 , 68, and 59 cm respectively. The clinical features included melanosis oris (Fig. l), severe bilateral gynecomastia (Tanner's Stage 111) with immature nipples, and large testes for his age (Tanner's Stage 11-111) measuring 3.5 x 2.0 cm, but with normal morphology and consistency. The penis was normal without evidence of precocious virilization. Ophthalmologically , the propositus showed nonaccomodative alternate esotropia. Laboratory StudiesLaboratory studies including urinalysis, blood cell count, plasma glucose, urea and creatinine, liver ...

Inappropriate authorship and other fraudulent publication strategies are pervasive. Here, I deal with contribution disclosures, authorship disputes versus plagiarism among collaborators, kin co-authorship, gender bias, authorship trade, and fake peer review (FPR). In contrast to underserved authorship and other ubiquitous malpractices, authorship trade and FPR appear to concentrate in some Asian countries that exhibit a mixed academic pattern of rapid growth and poor ethics. It seems that strong pressures to publish coupled with the incessantly growing number of publications entail a lower quality of published science in part attributable to a poor, compromised or even absent (in predatory journals) peer review. In this regard, the commitment of Publons to strengthen this fundamental process and ultimately ensure the quality and integrity of the published articles is laudable. Because the many recommendations for adherence to authorship guidelines and rules of honest and transparent research reporting have been rather ineffective, strong deterrents should be established to end manipulated peer review, undeserved authorship, and related fakeries.