Using MS-MLPA as an efficient screening tool for detecting 9p21 abnormalities in pediatric acute lymphoblastic leukemia.

Background: Characterization of recurrent genetic lesions in childhood acute lymphoblastic leukemia (ALL) has enabled therapeutic stratification with improved outcomes. The tumor suppressor genes, CDKN2A and CDKN2B, encoding p16(INK4a) , p14(ARF) , and p15(INK4b) have been localized to 9p21. Abnormalities of 9p21 have been reported in 10-30% of childhood ALL using conventional cytogenetics and fluorescence in situ hybridization (FISH).

Multiplex ligation-dependent probe amplification versus multiprobe fluorescence in situ hybridization to detect genomic aberrations in chronic lymphocytic leukemia: a tertiary center experience.

Cytogenetic abnormalities play a major role in the prognosis of patients with chronic lymphocytic leukemia (CLL). Several methods have emerged to try to best identify these abnormalities. We used fluorescence in situ hybridization (FISH) to determine the frequency of cytogenetic changes in our CLL patient population.

JAK2 V617F positive polycythemia Vera in a child with neurofibromatosis type I.

We report a child with polycythemia vera (PV). This patient demonstrates the acquired somatic JAK2 V617F mutation and also has neurofibromatosis type I (NF1). NF1, while not previously associated with PV, is associated with another childhood MPD, juvenile myelomonocytic leukemia (JMML).

Is gene discovery research or diagnosis?

The criteria that distinguish human genetic research from clinical molecular diagnosis are frequently practical rather than theoretical. They are driven by the availability and costs of the relevant technologies and the systemic level of scientific fluency in interpreting laboratory results. The guiding principle in the practice of medicine is the primacy of patient care.

VHL P25L is not a pathogenic von Hippel-Lindau mutation: a family study.

Background: von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome in which affected individuals may develop CNS and retinal hemangioblastomas, pheochromocytomas, renal cell carcinoma, and cysts of various organs. The VHL gene has been localized to chromosome 3p25-26 and >500 germline mutations have been identified. A rare variant of the VHL gene results in the substitution of lysine for proline at position 25 (P25L) in the larger of the two VHL proteins.

Congenital isolated adrenocorticotropin deficiency: an underestimated cause of neonatal death, explained by TPIT gene mutations.

Tpit is a T box transcription factor important for terminal differentiation of pituitary proopiomelanocortin-expressing cells. We demonstrated that human and mouse mutations of the TPIT gene cause a neonatal-onset form of congenital isolated ACTH deficiency (IAD). In the absence of glucocorticoid replacement, IAD can lead to neonatal death by acute adrenal insufficiency.

Spectrum of HNF1A and GCK mutations in Canadian families with maturity-onset diabetes of the young (MODY).

Purpose: Maturity-onset diabetes of the young (MODY) is a subtype of type 2 diabetes characterized by autosomal-dominant inheritance and early onset. The pathophysiology of MODY is primarily defective insulin secretion resulting from mutations in at least 6 different genes. Most affected patients harbour mutations in either GCK (encoding glucokinase, also called MODY2) and HNF1A (encoding hepatic nuclear factor-1alpha, also called MODY3).

ING1 and p53 tumor suppressor gene alterations in adenocarcinomas of the esophagogastric junction.

The aim of this study was to characterize molecular alterations of the recently reported candidate tumor suppressor gene, ING1, and to explore the relationship between ING1 and p53 in a well-defined series of adenocarcinomas of the esophagogastric junction (AdEGJ). Polymerase chain reaction (PCR)-based assays were used to characterize ING1 and p53 alterations, relative to histologically normal esophageal mucosa. Two tumors were found to have ING1 mutations: one novel missense mutation (AGC(Ser)-->ATC(Ile)) at codon 147, and one silent mutation (TCG(Ser)-->TCA(Ser)) at codon 173.

Association between Breus' mole and partial hydatidiform mole: chance or can hydropic villi precipitate placental massive subchorionic thrombosis?

Breus' mole (massive subchorionic hematoma) is a rare entity most often found in the placentae of macerated stillborn fetuses. Previously considered to represent a postmortem event, recent evidence suggests that it occurs prior to fetal demise. A 23-week gestation male neonate was delivered of a 23-year-old gravida 3, para 2 woman and survived for 49 min.