Rare etiology of autosomal recessive disease in a child with noncarrier parents

A child with maple syrup urine disease type 2 (MSUD2) was found to be homozygous for a 10-bp MSUD2-gene deletion on chromosome 1. Both purported parents were tested, and neither carries the gene deletion. Polymorphic simple-sequence repeat analyses at 15 loci on chromosome 1 and at 16 loci on other chromosomes confirmed parentage and revealed that a de novo mutation prior to maternal meiosis I, followed by nondisjunction in maternal meiosis II, resulted in an oocyte with two copies of the de novo mutant allele. Fertilization by a sperm that did not carry a paternal chromosome 1 or subsequent mitotic loss of the paternal chromosome 1 resulted in the propositus inheriting two mutant MSUD2 alleles on two maternal number 1 chromosomes.     

Supernumerary chromosome der(22)t(11;22): Emanuel syndrome associates with novel features

Emanuel syndrome results from +der(22)t(11q23;22q11). Cleft palate, ear anomalies, heart defects, genital anomalies, hypotonia, and mental retardation are the main features of the syndrome. We report a nine-year-old boy with the t(11;22)(q23;q11) chromosome, transmitted in an unbalanced fashion from his mother, and originated in the maternal grandmother's meiosis. In addition to mental retardation, hypotonia, craniofacial anomalies, and cryptorchidism, he has novel findings such as, joint hyperextensibility, left liver lobe agenesis, left sided malposition of the gallbladder and pancreas hypoplasia. This is the first report associating these features with Emanuel syndrome.     

Palaeobathymetric reconstruction of peritidal carbonates: Late Barremian, Urgonian, sequences of Provence (SE France)

Peritidal platform carbonates of Late Barremian age (Early Cretaceous) cropping out in the Marseille region (Provence, SE France) tend to be arranged stratigraphically in deepening-up or shallowing-up sequences. Seven facies types (lithofacies) were defined in the studied stratigraphic interval, ranging from supratidal to shallow subtidal settings. There is a good correspondence between the inferred relative water depth of facies and their average bed thickness. Cumulative thickness of facies types expresses quantitatively their palaeobathymetric range and provides an estimate of their average water depth. Calculations show that the palaeobathymetry of supratidal/intertidal facies types is from 0 to 40 cm, i.e. a pertaining to a palaeotidal (microtidal) range. The average palaeobathymetry of rudist facies, ascribed to subtidal settings, fluctuates between 40 cm and nearly 160 cm. Measuring a large number of beds belonging to both shallowing-up and deepening-up sequences, and averaging the results, appear relevant to minimise the effect of compaction, pressure solution and synsedimentary progressive or abrupt changes in accommodation, which are expected to modify bed thickness and its original palaeobathymetric significance. The method proposed here has a good potential for palaeobathymetric reconstruction of ancient peritidal carbonates.     

Trisomy 9p syndrome in two brothers: with new clinical findings and review of the literature

We report an eleven years old boy and his fourteen years old brother who both have trisomy 9p syndrome. Their cytogenetic analysis using GTL-banding showed 46,XY,der(22)add(22)(p11) karyotype. Cytogenetic analysis of their mother and sister revealed a karyogram designated as 46,XX,t(9;22) (9pter-->9p12::22p11-->22qter). With the help of FISH technique, the derivative chromosome in the proband was further confirmed to be a translocation chromosome 22 carrying the aforementioned segments from chromosome 9 which originated from a segregation event of a mother's balanced translocation. Regarding clinical aspects of our cases, both showed similar findings of 9p trisomy syndrome but low frontal hairline, circular placement of the hair around the face and scarce, inverted eyebrows, findings not previously mentioned in the literature. We conclude that these new clinical findings could be used in the clinical diagnosis of the 9p trisomy syndrome along with the other well-documented symptoms.     

Joubert syndrome co-existing with partial Xp trisomy: review of the literature

We report a five-year-old girl who has been clinically diagnosed as Joubert syndrome. Her cytogenetic analysis showed 46,XX,der(2)add(2q37) karyotype. Cytogenetic analysis of her mother and maternal grandmother revealed a karyogram designated as 46,X,t (X;2)(p11.2;q37). The proband's derivative chromosome was further confirmed to be a translocation chromosome 2 carrying segments from chromosome X, which originated from a segregation event of the maternal grandmother's balanced translocation passed on as a balanced translocation to the proband's mother either. So far, a number of candidate genes including EN1 on 2q were analyzed for Joubert syndrome. Based on our proband's abnormal karyotype, we suggest that further mapping studies for the syndrome should also be directed towards the chromosome X segments present on the derivative chromosome 2 of our proband.     

Evolution of the rudist bivalve Agriopleura Kühn (Radiolitidae,Hippuritida) from the Mediterranean region

The genus Agriopleura (Radiolitidae) is restricted to the Lower Cretaceous of the Mediterranean region, including the Middle East, and this rudist is apparently absent from the New World. Agriopleura underwent a size increase from late Hauterivian to mid‐late Barremian, matching Cope's rule, followed by a Lilliput phase in the early Aptian. The relative development of radial bands increased through time and represents a key evolutionary index. During its evolution, Agriopleura increased in species diversity and expanded geographically onto the European Mediterranean Tethyan margin from the late Hauterivian to Barremian, after which it disappeared from the region (pseudotermination). In the lower Aptian, after a Lazarus gap, the genus reappears in the southern Mediterranean Tethyan margin. Assuming that Archaeoradiolites is the direct descendant of Agriopleura, the disappearance of the genus in the mid‐Aptian was a pseudoextinction and this coincided with a major crisis of shallow carbonate settings and their associated biota. The definition of Agriopleura species is based on a set of qualitative and quantitative external and internal characters. Five species are recognized: three Barremian species, Agriopleura blumenbachi, the type species, A. marticensis and A. carinata; one lower Aptian species A. libanica; and a new species A. sequana restricted to the upper Hauterivian. Principal component analysis is used to test the distinctiveness of the species and the pattern of relationships of some of their key quantitative characters.     

A molecular characterization of the charismatic Faroe house mouse

Faroe house mice are a ‘classic’ system of rapid and dramatic morphological divergence highlighted by J. S. Huxley during the development of the Modern Synthesis. In the present study, we characterize these charismatic mice using modern molecular techniques, examining specimens from all Faroe islands occupied by mice. The aims were to classify the mice within the modern house mouse taxonomy (i.e. as either Mus musculus domesticus or Mus musculus musculus) using four molecular markers and a morphological feature, and to examine the genetic diversity and possible routes of colonization using mitochondrial (mt) control region DNA sequences and microsatellite data (15 loci). Mice on the most remote islands were characterized as M. m. domesticus and exhibited exceptionally low genetic diversity, whereas those on better connected islands were more genetically diverse and had both M. m. musculus and M. m. domesticus genetic elements, including one population which was morphologically M. m. musculus‐like. The mtDNA data indicate that the majority of the mice had their origins in south‐western Norway (or possibly southern Denmark/northern Germany), and probably arrived with the Vikings, earlier than suggested by Huxley. The M. m. musculus genetic component appears to derive from recent mouse immigration from Denmark. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 102 , 471–482.     

CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders

Joubert syndrome–related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MTS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-Löken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies.     

Identification of structural DNA variations in human cell cultures after long-term passage

Random amplified polymorphic DNA (RAPD) analysis was adapted for genomic identification of cell cultures and evaluation of DNA stability in cells of different origin at different culture passages. DNA stability was observed in cultures after no more than 5 passages. Adipose-derived stromal cells demonstrated increased DNA instability. RAPD fragments from different cell lines after different number of passages were cloned and sequenced. The chromosomal localization of these fragments was identified and single-nucleotide variations in RAPD fragments isolated from cell lines after 8–12 passages were revealed. Some of them had permanent localization, while most variations demonstrated random distribution and can be considered as de novo mutations.