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Although human amniotic fluid does contain different populations of foetal-derived stem cells, scanty information is available on the stemness and the potential immunomodulatory activity of in vitro expanded, amniotic fluid stem cells. By means of a methodology unrequiring immune selection, we isolated and characterized different stem cell types from second-trimester human amniotic fluid samples (human amniotic fluid stem cells, HASCs). Of those populations, one was characterized by a fast doubling time, and cells were thus designated as fHASCs. Cells maintained their original phenotype under prolonged in vitro passaging, and they were able to originate embryoid bodies. Moreover, fHASCs exhibited regulatory properties when treated with interferon ( IFN)-γ, including induction of the immunomodulatory enzyme indoleamine 2,3-dioxygenase 1 ( IDO1). On coculture with human peripheral blood mononuclear cells, IFN-γ-treated fHASCs caused significantly decreased T-cell proliferation and increased frequency in CD4+ CD25+ FOXP3+ regulatory T cells. Both effects required an intact IDO1 function and were cell contact-independent. An unprecedented finding in our study was that purified vesicles from IFN-γ-treated fHASCs abundantly expressed the functional IDO1 protein, and those vesicles were endowed with an fHASC-like regulatory function. In vivo, fHASCs were capable of immunoregulatory function, promoting allograft survival in a mouse model of allogeneic skin transplantation. This was concurrent with the expansion of CD4+ CD25+ Foxp3+ T cells in graft-draining lymph nodes from recipient mice. Thus fHASCs, or vesicles thereof, may represent a novel opportunity for immunoregulatory maneuvers both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The most frequent causes of Intellectual Disability (ID)/Autism Spectrum Disorders (ASDs) are chromosomal abnormalities, genomic rearrangements and submicroscopic deletions coupled with duplications. We report here on an 11-year-old girl showing autism, macrocephaly, and facial dysmorphism, in which array-CGH showed a de novo microdeletion of ∼114 Kb in the 14q11.2 chromosomal region, involving the SUPT16H, CHD8, and RAB2B genes. Four patients with ID and/or ASD and/or macrocephaly with overlapping deletions have been previously described: three showed very large rearrangements (>1 Mb), while one had a microdeletion of ∼101 Kb, largely overlapping the one reported herein. The minimal critical region, considering present and previous cases, contains the SUPT16H and CHD8 genes. Notably, recent studies also disclosed CHD8 heterozygous loss-of-function mutations in patients with ASD and macrocephaly. Our finding shows the presence of a recurrent microdeletion associated with a clinically recognizable phenotype, and further on underlines the pivotal role of CHD8 gene in the pathogenesis of the disorder. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Nablus mask-like facial syndrome (NMLFS) has many distinctive phenotypic features, particularly tight glistening skin with reduced facial expression, blepharophimosis, telecanthus, bulky nasal tip, abnormal external ear architecture, upswept frontal hairline, and sparse eyebrows. Over the last few years, several individuals with NMLFS have been reported to have a microdeletion of 8q21.3q22.1, demonstrated by microarray analysis. The minimal overlapping region is 93.98-96.22 Mb (hg19). Here we present clinical and microarray data from five singletons and two mother-child pairs who have heterozygous deletions significantly overlapping the region associated with NMLFS. Notably, while one mother and child were said to have mild tightening of facial skin, none of these individuals exhibited reduced facial expression or the classical facial phenotype of NMLFS. These findings indicate that deletion of the 8q21.3q22.1 region is necessary but not sufficient for development of the NMLFS. We discuss possible genetic mechanisms underlying the complex pattern of inheritance for this condition. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare condition belonging to the group of ectodermal dysplasias caused by TP63 mutations. Its clinical phenotype is similar to ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) and limb-mammary syndrome (LMS), and differs from these disorders mainly by the absence of cleft lip and/or palate. We report on a 39-year-old patient who was found to be heterozygous for a c.401G > T (p.Gly134Val) de novo mutation of TP63. This patient had the ADULT phenotype associated with cleft palate. Our findings, rather than extend the clinical spectrum of ADULT syndrome, suggest that cleft palate can no longer be considered an element for differential diagnosis for ADULT, EEC, and LMS. Our data, added to other reports on overlapping phenotypes, support the combining of these three phenotypes into a unique entity that we propose to call 'ELA syndrome,' which is an acronym of ectrodactyly-ectodermal dysplasia-cleft lip and palate, limb-mammary, and ADULT syndromes. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We report on a 9-year-old female patient with facial anomalies and developmental delay, heterozygous for three de novo rearrangements: a paracentric inversion of chromosome 7, an apparently balanced translocation between chromosome 1 and 7, involving the same inverted chromosome 7, detected by standard cytogenetic analysis [46,XX, der(7) inv(7)(q21.1q32.1)t(1;7)(q23q32.1)]; and a 2p16.1 deletion, spanning about 3.5 Mb of genomic DNA, shown by SNP-array analysis [arr 2p16.1 (56,706,666-60,234,485)x1 dn]. Clinical features and cytogenetic imbalance in our patient were similar to those reported in five published cases, suggesting that this genomic region is prone to recombination and its hemizygosity results in a distinct although variable spectrum of clinical manifestations. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We describe a 4-year-old female child with severe global mental retardation, myoclonic epilepsy, proximal hypotonia and dysmorphisms, whose prenatal diagnosis following amniocentesis revealed a constitutional female karyotype carrying a t(1;15)(q10;p11) familial reciprocal translocation. Post-natal high-resolution karyotype, Fluorescence in situ hybridization (FISH) screening for subtelomeric rearrangements, VNTR search for UPD15 in the blood and fibroblast, and WCP1 and 15 in the mother, failed to provide an explanation for the complex clinical phenotype of the proband. Since the pachytene configuration of the translocated chromosomes defines a high probability of 3:1 segregation, an extensive workup was undertaken to look for a possibly cryptic mosaicism. Four percent of the cells with trisomy 15 was found in the peripheral blood lymphocytes examined by classical cytogenetic technique and interphase FISH analysis. The clinical features associated with cryptic trisomy 15 mosaicism and the problems concerning prenatal diagnosis and genetic counselling for carriers of translocations at high risk of 3:1 segregation are discussed. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Craniotubular dysplasias (CTD) are a heterogeneous group of genetic disorders of skeletal development, whose clinical and etiological classification is still much debated. One of the most common form is the autosomal dominant craniometaphyseal dysplasia (CMD) which is associated with mutation in the ANKH gene. In the literature a few families are reported with CMD phenotype that suggest an autosomal recessive (AR) pattern of inheritance. A candidate locus at 6q21-22 has been mapped in a large inbred Brazilian family, but the gene of the recessive form is still unknown. Our data on a female patient with CMD phenotype, born from healthy first degree cousins and displaying homozygosity for polymorphic markers at the 6q21-22 locus, further support the existence of an AR CMD, expanding its clinical spectrum to a more severe phenotype. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A letter to the editor discussing the occurrence of the same chromosome abnormalities in Ph+ and Ph− cells in chronic myeloid leukaemia is presented.

Carney complex (CNC) is an inherited autosomal dominant disorder associated with multiple neoplasms. Myxomas associated with CNC differ from their sporadic forms because the former usually develop at a younger age and they may be multicentric and have a tendency to recur. Furthermore, their localization may be atypical. We report the case of a 57-year-old man, with a huge right atrial myxoma obstructing the tricuspid valve orifice. A diagnosis of CNC was established by genetic analysis. The importance of early diagnosis and an adequate follow-up is emphasized., (© 2010 Wiley Periodicals, Inc.)

A 36-year-old patient with a disorder characterized by severe mental retardation, behavioral problems, dysmorphic face, "muscular build," and hand/foot anomalies, is reported. Following a diagnosis of de novo pericentric inversion of chromosome 8 based on standard cytogenetic analysis, a subsequent 75 kb array-CGH investigation disclosed a deletion spanning for about 13.7 Mb in the 2q31.2q32.3 region. Whole painting of chromosome 8 established the intrachromosomal nature of the rearrangement and FISH analysis with locus-specific probes confirmed the deletion on the long arm of chromosome 2. The deleted region, clinical outcome, and medical history in this patient are mainly superimposable to those reported in a published 8-year-old boy, suggesting that this genomic segment is prone to rearrangements and its hemizygosity gives rise to a clinically recognizable syndrome. The role of some genes mapping in the deleted region and related with distinct disorders is discussed. Interestingly, deletion of MSTN gene, a negative regulator of muscle growth, was associated in our patient with a "muscular build," a feature which could be regarded as a handle for clinical recognition of this syndrome.