Medical genetics

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38266/1/28_ftp.pd

Ehlers–Danlos syndrome, hypermobility type: A characterization of the patients' lived experience

Hypermobility type Ehlers–Danlos syndrome (EDS‐HT) is an inherited connective tissue disorder clinically diagnosed by the presence of significant joint hypermobility and associated skin manifestations. This article presents a large‐scale study that reports the lived experience of EDS‐HT patients, the broad range of symptoms that individuals with EDS‐HT experience, and the impact these symptoms have on daily functioning. A 237‐item online survey, including validated questions regarding pain and depression, was developed. Four hundred sixty‐six (466) adults (90% female, 52% college or higher degree) with a self‐reported diagnosis of EDS‐HT made in a clinic or hospital were included. The most frequently reported symptoms were joint pain (99%), hypermobility (99%), and limb pain (91%). They also reported a high frequency of other conditions including chronic fatigue (82%), anxiety (73%), depression (69%), and fibromyalgia (42%). Forty‐six percent of respondents reported constant pain often described as aching and tiring/exhausting. Despite multiple interventions and therapies, many individuals (53%) indicated that their diagnosis negatively affected their ability to work or attend school. Our results show that individuals with EDS‐HT can experience a wide array of symptoms and co‐morbid conditions. The degree of constant pain and disability experienced by the majority of EDS‐HT respondents is striking and illustrates the impact this disorder has on quality of life as well as the clinical challenges inherent in managing this complex connective tissue disorder. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101781/1/ajmga36293.pd

Quality of Life and Autonomy in Emerging Adults with Early‐Onset Neuromuscular Disorders

Emerging adulthood is an important period in the development of one’s identity and autonomy. The ways in which identity and autonomy are viewed by emerging adults and how they impact quality of life (QoL) in individuals with early‐onset neuromuscular conditions is not yet known. This study focused on understanding and exploring relationships between self‐perceptions of emerging adulthood, autonomy, and QoL. Five previously validated measures were incorporated into an online survey and distributed to young adults with early‐onset neuromuscular conditions and unaffected controls. Topics explored included individuals’ views regarding their overall QoL, disease‐specific QoL, components of emerging adulthood, and autonomy. We found that a sense of higher disease impact was associated with a lower Overall General QoL. Additionally, perceptions of key autonomy factors “negativity” and “instability” were uniquely associated with Overall General QoL in the case group as compared to controls, whereas “attitudinal autonomy” (attaining the ability to plan and follow through with goals) was important to this age group regardless of health status. The specific factors of emerging adulthood and autonomy that were significantly correlated with Overall General QoL can be used for developing targeted counseling and interventions to improve QoL for individuals and their families.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146967/1/jgc40713.pd

Overexpressed Genes/ESTs and Characterization of Distinct Amplicons on 17823 in Breast Cancer Cells

Abstract17823 is a frequent site of gene amplification in breast cancer. Several lines of evidence suggest the presence of multiple amplicons on 17823. To characterize distinct amplicons on 17823 and localize putative oncogenes, we screened genes and expressed sequence tags (ESTs) in existing physical and radiation hybrid maps for amplification and overexpression in breast cancer cell lines by semiquantitative duplex PCR, semiquantitative duplex RT-PCR, Southern blot, Northern blot analyses. We identified two distinct amplicons on 17823, one including TBX2 and another proximal region including RPS6KB1 (PS6K) and MUL. In addition to these previously reported overexpressed genes, we also identified amplification and overexpression of additional uncharacterized genes and ESTs, some of which suggest potential oncogenic activity. In conclusion, we have further defined two distinct regions of gene amplification and overexpression on 17823 with identification of new potential oncogene candidates. Based on the amplification and overexpression patterns of known and as of yet unrecognized genes on 17823, it is likely that some of these genes mapping to the discrete amplicons function as oncogenes and contribute to tumor progression in breast cancer cells

CHFR (Checkpoint with fork-head associated and ring finger)

Growing evidence in mice, primary human tumors, and mammalian cell culture models indicate that CHFR may function as a potent tumor suppressor. CHFR functions as part of an early G2/M checkpoint, more specifically in antephase. Antephase refers to late G2 when chromosome condensation starts. This early mitotic checkpoint causes a delay in chromosome condensation in response to mitotic stresses. The human CHFR gene was originally identified during a search for novel cell cycle checkpoint proteins that have fork-head associated domains. Initial analysis indicated that the CHFR-associated G2/M checkpoint was inactivated in a subset of cancers as demonstrated by high mitotic indices (a high percentage of cells that have condensed chromosomes) in response to exposure to the microtubule poison, nocodazole, due to lack of CHFR expression or CHFR mutations in various cancers. Many other studies showed promoter hypermethylation leading to low/no expression of CHFR

Malignant triton tumor in a patient with Li-Fraumeni syndrome and a novel TP53 mutation

We report a 3-year-old boy with a malignant triton tumor (MTT) involving the left masticator space with local invasion and regional lymph node metastasis. Family history and detection of a novel germline TP53 mutation confirmed his diagnosis of Li Fraumeni syndrome (LFS). MTT has not been previously described in association with LFS. This case along with a comprehensive review of the literature, illustrate the importance of both somatic and germline TP53 mutations in the pathogenesis MTT. The tumor could not be resected and he was successfully treated with intensive induction chemotherapy, irradiation, and high-dose chemotherapy with autologous stem cell transplantation. © 2005 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35300/1/20700_fta.pd

High rates of unsuccessful transfer to adult care among young adults with juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>This study aimed to describe the proportion of patients with juvenile idiopathic arthritis (JIA) who had experienced an unsuccessful transfer from a pediatric rheumatology team to an adult rheumatologist and to compare the characteristics of those who achieved successful transfer to those who did not.</p> <p>Methods</p> <p>We conducted a systematic chart review of all patients with JIA who attended their final Montreal Children's Hospital JIA clinic appointment between 1992 and 2005. We tracked these patients for the two years after transfer to an adult rheumatologist. We then compared characteristics of patients with successful and unsuccessful transfers of care. Variables pertaining to disease characteristics, disease severity and psychosocial factors were examined. Univariate analyses were performed to determine if any single factor was associated with the outcome of unsuccessful transfer of care.</p> <p>Results</p> <p>52% of patients fulfilled our criteria for unsuccessful transfer. Of the variables tested, an active joint count (AJC) of zero at last visit was associated with the outcome of unsuccessful transfer (OR = 2.67 (CI 1.16-6.16; p = 0.0199)).</p> <p>Conclusions</p> <p>Despite the presence of a coordinated process of transfer from pediatric to adult health care for the majority of the patients in this study, there was a high rate of unsuccessful transfer and/or sustained follow up which is disheartening. We found that patients with less active disease at the time of transfer, as indicated by a lower AJC, were more likely to be lost to follow up. Recent literature suggests that even in the least severe categories of JIA, 50% of patients persist with active disease into adulthood. Thus educating all JIA patients about the possibility of disease flare in adulthood may improve their adherence to recommendations for sustained follow-up in the adult milieu. This may lead to improvement of longitudinal outcomes for all JIA patients.</p