MLL-MLLT10 fusion in acute monoblastic leukemia: variant complex rearrangements and 11q proximal breakpoint heterogeneity

Cytogenetic studies of acute monoblastic leukemia cases presenting MLL-MLLT10 (alias MLL-AF10) fusion show a broad heterogeneity of chromosomal breakpoints. We present two new pediatric cases (French-American-British type M5) with MLL-MLLT10 fusion, which we studied with fluorescence in situ hybridization. In both we detected a paracentric inversion of the 11q region that translocated onto chromosome 10p12; one case displayed a variant complex pattern. We review the cytogenetic molecular data concerning the proximal inversion breakpoint of 11q and confirm its heterogeneit

MEIOTIC ORIGIN OF TRISOMY IN NEOPLASM: EVIDENCE IN A CASE OF ERYTROLEUKAEMIA

Trisomic cells in neoplasms may represent abnormal clones originated from a tissue-confined mosaicism, and arise therefore by a meiotic error. We report on a 16-month-old child with erythroleukaemia (AML-M6), whose marrow karyotype at onset was 48,XX,del(13)(q12q14),del(14)(q22q32),+21,+21. The parental origin of the supernumerary chromosomes 21 was investigated by comparing 10 polymorphic loci scattered along the whole chromosome on the patient's marrow and her parents' leukocytes. Three loci were informative for the presence of three alleles, two of which were of maternal origin; two further loci showed a maternal allele of higher intensity. Lymphocytes and skin fibroblasts showed a normal karyotype, and molecular analysis on leukocytes at remission, buccal smear and urinary sediment cells consistently showed only one maternal allele, whereas neonatal blood from Guthrie spot showed two maternal alleles as in the marrow. An accurate clinical re-evaluation confirmed a normal phenotype. Our results indicate that tetrasomy 21 arose from a marrow clone with trisomy 21 of meiotic origin. To the best of our knowledge, this is the first evidence that supernumerary chromosomes in neoplastic clones may in fact be present due to a meiotic error. This demonstrates that a tissue-confined constitutional mosaicism for a trisomy may indeed represent the first event in multistep carcinogenesis

Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

ObjectiveProinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology.Research design and methodsWe have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates.ResultsNine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets.ConclusionsWe have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

A new incision in the correction of radial longitudinal deficiency: The double Y sliding flap approach

One concern in the surgical treatment of radial longitudinal deficiency (RLD) is certainly the skin incision. Over the years many different types have been proposed and used. We propose a new skin incision technique: a double Y sliding flap with the main body along the dorsal wrist crease, followed by raising a proximal and a distal flap providing wide access to the dorsal surface of the wrist joint. After correction of the wrist deformity, skin triangles are resected on the radial and ulnar sides of the incision. Then the skin of the distal flap is slid radially and proximally, filling the defect left by the resected radial triangle, while the proximal flap is slid in the opposite direction, enabling transverse closure along the ulnar side of the incision. The final scar comprises a central body along the dorsal wrist crease, and a radial branch. The aim of this study was to analyze the clinical results of this new double Y sliding flap approach for the surgical treatment of type III and IV RLD. We retrospectively reviewed medical records of surgical correction of RLD using our new incision, between January 2016 and December 2018 in our department of hand surgery. Endpoints comprised correction of redundant skin, scar appearance, and complications. Twelve limbs in 9 patients treated with this double Y sliding flap approach were reviewed: correction of redundant skin was systematic, only 2 limbs showed postoperative complications (1 case of notable edema and 1 of delayed wound healing), and scar aspect was graded good in 11 of the 12 cases. The double Y sliding flap was safe, with minimal complications, adequate skin restoration, wide exposure of the wrist, and esthetically good scar. (c) 2022 SFCM. Published by Elsevier Masson SAS. All rights reserved

’The hand of the child’ Campus: an opportunity to meet, play and compare.

Questo contributo è una presentazione svolta al Convegno Europeo della FESSH (Federation of the European Societies for Surgery of the Hand) in occasione dell'EXPO di Milano, che ha raccolto a livello europeo e mondiale i maggiori esperti di chirurgia della mano a Milano. Il lavoro presentato ha focalizzato alcune problematiche legate alle malformazioni congenite e traumi nei bambini e all'esperienza svolta in diverse edizioni del Campus, organizzato dall'Unità Operativa di Chirurgia della mano dell'Ospedale San Giuseppe di Milano. Tale esperienza, condotta in modo interdisciplinare da chirurghi, fisioterapisti e psicologi, è volta in modo particolare a promuovere un'esperienza di mutuo-aiuto, supportata da esperti psicologi, sulle problematiche psicologiche dei familiari e dei bambini, in termini di socializzazione, accettazione del sè, comunicazione medico-paziente