Isodicentric/pseudoisodicentric chromosome 21 amplification in four cases of acute myelocytic leukemia or myelodysplasia

The bone marrow karyotypes of three patients with acute myelocytic leukemia (AML) or myelodysplastic syndrome (MDS) were studied at diagnosis and revealed, multiple copies of the same chromosomal anomaly, considered as psu idic(21)(q22) associated with other rearrangement(s). The karyotype of a fourth patient with MDS in transformation showed one copy of a dicentric marker presumably derived from a similar psu idic(21) by (tandem?) interstitial amplification of part of its structure, resembling a "homogeneous staining region", and described as der(21)psu idic(21)(q22)hsr(21)(q22). This rearrangement, previously described in isolated cases only, might be considered as recurrent in AML/MDS and associated with an unfavorable prognosis. It is most probably a secondary change, because it was never observed as sole abnormality and the main association, as for trisomy 21, was with del(5q). In the four cases, the number of partial supernumerary segmental 21pter-->21q22 copies, ranged from 2 to 10. The AML1 gene did not appear to be the common target of this amplification because this locus had been lost by the psu idic(21) in one patient     

Lipid profile,inflammation, and oxidative status in peri- and postmenopausal women

Objective: To evaluate the effect of perimenopause and postmenopause on lipid profile, inflammation, and oxidative stress in women.

Methods: This cross-sectional study included 117 women (47?±?6 years) classified as perimenopausal (n?=?47), postmenopausal (n?=?40), or non-menopausal (n?=?30). In serum, we analyzed lipid profile, tumor necrosis factor-alpha (TNF-α), interleukin-1α (IL-1α), and C-reactive protein (CRP). Pro-oxidant status was assessed by thiobarbituric acid reactive substances (TBARS) and protein carbonyls. Antioxidant defense was performed by analysis of superoxide dismutase (SOD) and catalase activities.

Results: Compared to non-menopausal women, triacylglycerols (TG) were similar, total cholesterol and LDL-C were higher in perimenopausal and postmenopausal women, while HDL-C concentrations were decreased. TNF-α and IL-1α were higher in postmenopausal women, while CRP concentrations were elevated in both peri-and postmenopausal women (p?p?p?Conclusion: Menopausal transition and postmenopause were associated with dyslipidemia, inflammation, and unbalanced oxidative status exposing women to cardiovascular risk.     

Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene

BACKGROUND: The first locus for demyelinating autosomal recessive Charcot-Marie-Tooth (ARCMT) disease was identified in 8q13, where mutations in GDAP1 have been found. Mutations in the same gene have been detected in families with axonal ARCMT disease. OBJECTIVE: To determine the clinical, electrophysiologic, and morphologic characteristics of a consanguineous Moroccan family with ARCMT disease associated with the S194X mutation in the GDAP1 gene. METHODS: Four patients from a consanguineous Moroccan family were examined clinically and electrophysiologically. In one patient, a morphometric and ultrastructural study of a peroneal nerve biopsy sample was performed. Mutation in the coding region of the GDAP1 gene was identified by direct sequencing. RESULTS: Neuropathy was evident early in childhood, walking was delayed in one patient, and onset of symptoms occurred before 18 months in the others. The phenotype was severe: foot deformities and disabilities involving the hands and feet developed toward the end of the first decade, followed by involvement of proximal muscles in the lower limbs, leading to loss of autonomy. Electrophysiologic findings were consistent with an axonal form of CMT disease: motor nerve conduction velocities, recordable in one patient only, were greater than 40 m/sec. Sensory nerve action potentials were either abolished or substantially reduced in amplitude. The morphologic data supported the diagnosis of axonal neuropathy, showing a marked reduction in myelinated fibers and signs of axonal regeneration, including frequent pseudo-onion bulb formations. The 4 patients in this family were homozygous for the S194X mutation in the GDAP1 gene. CONCLUSION: Electrophysiologic and pathological findings support the hypothesis of an axonal disorder in this ARCMT family with the S194X mutation in the GDAP1 gene.     

Paternal isodisomy for chromosome 2 as the cause of Crigler-Najjar type I syndrome

Crigler-Najjar syndrome type I (CN-I) is a rare and severe autosomal recessive metabolic disease due to a total deficiency of bilirubin uridine diphosphate glucuronosyltransferase located on chromosome 2. We report on a child with CN-I due to a phenylalanine residue deletion inherited only from the father carrying this deletion at the heterozygous state. Cytogenetic analyses showed no deletion of the chromosomal 2q37 region. Microsatellite analysis of the child and his parents was consistent with paternal isodisomy for chromosome 2 in the child. This report demonstrates that uniparental disomy may be at the origin of very rare diseases transmitted as autosomal recessive traits and emphasizes the need for parental DNA analysis in such cases.     

Surgical Treatment of Chronic Lateral Ankle Instability Using an Inferior Extensor Retinaculum Flap: A Retrospective Study

Chronic lateral ankle instability causes significant problems with physical activity. The purpose of the present study was to evaluate the results of ligamentous retensioning combined with reinforcement using an extensor retinaculum flap. A consecutive series of 38 patients were included with a minimum follow-up duration of 2 years. The functional results were assessed using the Karlsson and American Orthopaedic Foot and Ankle Society scale scores. The pre- and postoperative radiologic assessment was performed using stress radiographs to measure varus tilt and anterior drawer tests. All 38 patients were followed up for 2.5 to 7.2 years, and 35 patients were satisfied. The American Orthopaedic Foot and Ankle Society scale score had improved significantly from 57 (range 20 to 70) points preoperatively to 95 (range 80 to 100) points postoperatively (p < .0001), and 35 patients believed their ankle was more stable after surgery. The patients had returned to their previous sports activities an average of 4.7 (range 2 to 12) months after surgery. On the stress radiographs, the mean talar tilt angle had improved significantly from 15.2° (range 6° to 26°) preoperatively to 3.8° (range 1° to 8°) at the final follow-up visit (p < .001), and the mean anterior talar had improved significantly from 13.2 (range 8 to 18) mm preoperatively to 4 (range 4 to 7) mm at the final follow-up visit (p < .002). Regarding the prognostic factors, a link was found between the functional result and residual radiologic laxity measured on the stress radiographs. Reconstruction of the lateral ligaments for chronic ankle instability combining capsuloligamentous retensioning and reinforcement with an extensor retinaculum flap resulted in successful outcomes, excellent ankle stability, and preservation of ankle joint mobility. This technique addressed both lateral ankle and subtalar instability by developing an extraarticular interosseous ligament.