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Somatic Mosaicism (somatic + mosaicism)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Somatic APC mosaicism: a frequent cause of familial adenomatous polyposis (FAP),

HUMAN MUTATION, Issue 10 2007
Stefan Aretz
Abstract Somatic mutational mosaicism presents a challenge for both molecular and clinical diagnostics and may contribute to deviations from predicted genotype,phenotype correlations. During APC mutation screening in 1,248 unrelated patients with familial adenomatous polyposis (FAP), we identified 75 cases with an assumed or confirmed de novo mutation. Prescreening methods (protein truncation test [PTT], DHPLC) indicated the presence of somatic mosaicism in eight cases (11%). Sequencing of the corresponding fragments revealed very weak mutation signals, pointing to the presence of either nonsense or frameshift mutations at low level. All mutations were confirmed and quantified by SNaPshot analysis: in leukocyte DNA from the eight patients, the percentage of mosaicism varied between 5.5% and 77%, while the proportion of the mutation in DNA extracted from adenomas of the respective patient was consistently higher. The eight mutations identified as mosaic are localized within codons 216,1464 of the APC gene. According to the known genotype,phenotype correlation, patients with mutations in this region exhibit typical or severe FAP. However, six of the eight patients presented with an attenuated or atypical polyposis phenotype. Our data demonstrate that in a fraction of FAP patients the causative APC mutation may not be detected due to weak signals or somatic mosaicism that is restricted to tissues other than blood. SNaPshot analysis was proven to be an easy, rapid, and reliable method of confirming low-level mutations and evaluating the degree of mosaicism. Some of the deviations from the expected phenotype in FAP can be explained by the presence of somatic mosaicism. Hum Mutat 28(10), 985,992, 2007. © 2007 Wiley-Liss, Inc. [source]

Nonsyndromic mental retardation and cryptogenic epilepsy in women with Doublecortin gene mutations

ANNALS OF NEUROLOGY, Issue 1 2003
Renzo Guerrini MD
DCX mutations cause mental retardation in male subjects with lissencephalypachygyria and in female subjects with subcortical band heterotopia (SBH). We observed four families in which carrier women had normal brain magnetic resonance imaging (MRI) and mild mental retardation, with or without epilepsy. Affected male subjects had SBH or pachygyria-SBH. In two families, the phenotype was mild in both genders. In the first family, we found a tyr138his mutation that is predicted to result in abnormal folding in the small hinge region. In the second family, we found an arg178cys mutation at the initial portion of R2, in the putative ,-sheet structure. Carrier female subjects with normal MRI showed no somatic mosaicism or altered X-inactivation in lymphocytes, suggesting a correlation between mild mutations and phenotypes. In the two other families, with severely affected boys, we found arg76ser and arg56gly mutations within the R1 region that are predicted to affect DCX folding, severely modifying its activity. Both carrier mothers showed skewed X-inactivation, possibly explaining their mild phenotypes. Missense DCX mutations may manifest as non-syndromic mental retardation with cryptogenic epilepsy in female subjects and SBH in boys. Mutation analysis in mothers of affected children is mandatory, even when brain MRI is normal. Ann Neurol 2003 [source]

Vascular anomalies in Proteus syndrome

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2004
P. H. Hoeger
Summary Proteus syndrome (PS) is a complex hamartomatous disorder defined by local overgrowth (macrodactyly or hemihypertrophy), subcutaneous tumours and various bone, cutaneous and/or vascular anomalies (VA). VA are manifold in PS, but their prevalence is unknown so far. In order to further characterize PS, we studied the prevalence of VA in 22 PS patients presenting to our outpatient clinic and reviewed 100 PS patients previously reported between 1983 and 2001. The diagnosis of vascular abnormalities was made on clinical grounds and supported with imaging studies and/or histology in 12 and seven patients out of 22, respectively. Thirty-five VA were identified in 22/22 (100%) of our patients, and more than one type of VA were present in 10 of them. Vascular tumours, portwine stains (PWS), and venous anomalies (varicosities, prominent veins) were equally common. A total of 118 VA were previously reported in 70/100 (70%) PS patients; vascular hamartomas were more prevalent (56/118 = 47.5%), whilst PWS (21.2%) and venous anomalies (22.9%) were slightly less common than in our series, but there is the possibility of under-reporting. Unlike Klippel,Trenaunay syndrome, where VA are mostly confined to the hypertrophic limb, major arteriovenous anomalies are rare, and ,,similar to the other hamartomas and naevi observed in PS (pigmentary naevi, epidermal naevi, subcutaneous tumours, exostoses) , VA appear to be distributed at random sites on the body. We conclude that VA are among the most common findings in PS. Their varying type and distribution lend further support to the concept of somatic mosaicism. [source]

Congenital central hypoventilation syndrome: genotype,phenotype correlation in parents of affected children carrying a PHOX2B expansion mutation

CLINICAL GENETICS, Issue 3 2010
S Parodi
Parodi S, Vollono C, Baglietto MP, Balestri M, Di Duca M, Landri PA, Ceccherini I, Ottonello G, Cilio MR. Congenital central hypoventilation syndrome: genotype,phenotype correlation in parents of affected children carrying a PHOX2B expansion mutation. Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic disorder. Although most CCHS associated PHOX2B mutations occur de novo, about 10% of the cases are inherited from apparently asymptomatic parents, thus confirming variable expressivity and incomplete penetrance of PHOX2B mutations. Three asymptomatic parents of children affected with CCHS, and found to carry the same PHOX2B expansion mutations as their siblings, were studied by overnight polysomnography and somatic mosaicism analysis. In one case, significant sleep breathing control anomalies were detected, while the other two resulted in normal. In tissue-specific allele studies, mosaicism with a comparatively low mutant allele proportion was showed in the two unaffected adult carriers. Accurate polysomnography and assessment of the degree of somatic mosaicism should be conducted in asymptomatic carriers of PHOX2B mutations, as they may unmask subclinical but significant anomalies [source]