Jacobsen Syndrome: Surgical Complications due to Unsuspected Diagnosis, the Importance of Molecular Studies in Patients with Craniosynostosis.

Jacobsen syndrome (JBS) is an uncommon contiguous gene syndrome. About 85-92% of cases have a de novo origin. Clinical variability and severity probably depend on the size of the affected region. The typical clinical features in JBS include intellectual disability, growth retardation, craniofacial dysmorphism as well as craniosynostosis, congenital heart disease, and platelet abnormalities. The proband was a 1 year/3-month-old Mexican male. Oligonucleotide-SNP array analysis using the GeneChip Human Cytoscan HD was carried out for the patient from genomic DNA. The SNP array showed a 14.2-Mb deletion in chromosome 11q23.3q25 (120,706-134,938 Mb), which involved 163 RefSeq genes in the database of genomic variation. We report a novel deletion in JBS that increases the knowledge of the variability in the mutation sites in this region and expands the spectrum of molecular and clinical defects in this syndrome.

A Novel 23.1 Mb Interstitial Deletion Involving 7q22.3q32.1 in a Girl with Short Stature, Motor Delay, and Craniofacial Dysmorphism.

Interstitial deletions of 7q show a wide phenotypic spectrum that varies with respect to the location and size of the deleted region. They lead to craniofacial dysmorphism with intellectual disability, growth retardation, and various congenital defects. Here, a Mexican girl with microcephaly, facial dysmorphism, short stature, hand anomalies, and intellectual disability was analyzed by CytoScan HD array. Her phenotype was associated with a de novo 7q22.3q32.1 deletion involving 109 loci, 57 of them listed in the OMIM database. This novel deletion increases the knowledge of the variability in the rupture sites of the region and expands the spectrum of molecular and clinical defects of the 7q deletion syndrome.

Characterization of a Complex Chromosomal Rearrangement Involving a de novo Duplication of 9p and 9q and a Deletion of 9q.

Rearrangements of the distal region of 9p are important chromosome imbalances in human beings. Trisomy 9p is the fourth most frequent chromosome anomaly and is a clinically recognizable syndrome. Kleefstra syndrome, previously named 9q subtelomeric deletion syndrome, is either caused by a submicroscopic deletion in 9q34.3 or an intragenic mutation of EHMT1. We report a Mexican male patient with abnormal development, dysmorphism, systemic anomalies and a complex chromosomal rearrangement (CCR). GTG-banding revealed a 46,XY,add(9)(q34.3) karyotype, whereas array analysis resulted in arr[hg19] 9p24.3p23(203,861-11,842,172)×3, 9q34.3(138,959,881-139,753,294)×3, 9q34.3(139,784,913-141,020,389)×1. Array and karyotype analyses were normal in both parents. Partial duplication of 9p is one of the most commonly detected autosomal structural abnormalities in liveborn infants. A microdeletion in 9q34.3 corresponds to Kleefstra syndrome, whereas a microduplication in 9q34.3 shows a great clinical variability. Here, we present a CCR in a patient with multiple congenital anomalies who represents the first case with partial 9p trisomy, partial 9q trisomy and partial 9q monosomy.

A novel microdeletion involving the 13q31.3-q32.1 region in a patient with normal intelligence.

Microdeletions of the long arm of chromosome 13 lead to a characteristic facial appearance with systemic affection; 13q deletion shows a wide phenotypic spectrum that varies with respect to the location and size of the deletion region. The main clinical features are mental retardation, growth retardation, craniofacial dysmorphy and various congenital defects. In the present study we describe the case of an adult female of Mexican origin with microcephaly, facial dysmorphism, short stature, hand anomalies and normal intelligence associated with a de novo 13q31.3-q32.1 microdeletion that involved several genes including the MIR17HG and the GPC5 genes.

Noonan syndrome: prenatal diagnosis in a woman carrying a PTPN11 gene mutation.

OBJECTIVE: To describe the case of a pregnant woman and her fetus with Noonan syndrome (NS) whom were diagnosed through ultrasonography 3D and molecular analysis of the PTPN11 gene. STUDY DESIGN: Case report. RESULTS: We detected in a pregnant woman and her child the G

Functional analysis of myelodysplastic syndromes-derived mesenchymal stem cells.

Two different reports, including one from our own group, have recently demonstrated the presence of severe chromosomal abnormalities in mesenchymal stem cells (MSC) from patients with myelodysplastic syndromes (MDS). In the present study, we have assessed whether such cytogenetic abnormalities result in functional deficiencies in vitro. We found that both normal and MDS MSC showed similar expression patterns of cell adhesion molecules and extracellular matrix proteins. MDS MSC layers showed the capability to differentiate towards adipocytes, chondrocytes and osteoblasts, and supported the growth of early umbilical cord blood progenitors in a co-culture system. Unstimulated MDS MSC secreted more IL-1beta and after treatment with TNFalpha, they secreted more SCF, as compared to their normal counterparts. The present study demonstrates that, in spite of harboring severe chromosomal alterations, most of the functional properties of MDS-derived MSC remain normal, including their ability to support normal hematopoiesis in vitro.

Mesenchymal stem cells in myelodysplastic syndromes: phenotypic and cytogenetic characterization.

Bone marrow-derived mesenchymal stem cells (MSC) have been defined as primitive, undifferentiated cells, capable of self-renewal and with the ability to give rise to different cell lineages, including adipocytes, osteocytes, fibroblasts, chondrocytes, and myoblasts. MSC are key components of the hematopoietic microenvironment. Several studies, including some from our own group, suggest that important quantitative and functional alterations are present in the stroma of patients with myelodysplasia (MDS). However, in most of such studies the stroma has been analyzed as a complex network of different cell types and molecules, thus it has been difficult to identify and characterize the cell(s) type(s) that is (are) altered in MDS. In the present study, we have focused on the biological characterization of MSC from MDS. As a first approach, we have quantified their numbers in bone marrow, and have worked on their phenotypic (morphology and immunophenotype) and cytogenetic properties. MSC were obtained by a negative selection procedure and cultured in a MSC liquid culture medium. In terms of morphology, as well as the expression of certain cell markers, no differences were observed between MSC from MDS patients and those derived from normal marrow. In both cases, MSC expressed CD29, CD90, CD105 and Prolyl-4-hydroxylase; in contrast, they did not express CD14, CD34, CD68, or alkaline phosphatase. Interestingly, in five out of nine MDS patients, MSC developed in culture showed cytogenetic abnormalities, usually involving the loss of chromosomal material. All those five cases also showed cytogenetic abnormalities in their hematopoietic cells. Interestingly, in some cases there was a complete lack of overlap between the karyotypes of hematopoietic cells and MSC. To the best of our knowledge, the present study is the first in which a pure population of MSC from MDS patients is analyzed in terms of their whole karyotype and demonstrates that in a significant proportion of patients, MSC are cytogenetically abnormal. Although the reason of this is still unclear, such alterations may have an impact on the physiology of these cells. Further studies are needed to assess the functional integrity of MDS-derived MSC.