Postzygotic mutation and germline mosaicism in the otopalatodigital syndrome spectrum disorders. by Robertson, S, Thompson, S, Morgan, T, Holder-Espinasse, M, Martinot-Duquenoy, V, Wilkie, A, Manouvrier-Hanu, S

“…The mutation is not detectable in the blood leucocytes of their clinically unaffected mother, indicating that she is a germline mosaic for the condition. The description of somatic mutations and germline mosaicism in FLNA has implications for clinical and molecular diagnosis, phenotypic expression and genetic counseling of families with these disorders.…”

Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism. by Twigg, S, Ousager, L, Miller, K, Zhou, Y, Elalaoui, S, Sefiani, A, Bak, G, Hove, H, Hansen, L, Fagerberg, C, Tajir, M, Wilkie, A

“…In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. …”

The origin of EFNB1 mutations in craniofrontonasal syndrome: frequent somatic mosaicism and explanation of the paucity of carrier males. by Twigg, SR, Matsumoto, K, Kidd, A, Goriely, A, Taylor, I, Fisher, R, Hoogeboom, A, Mathijssen, I, Lourenco, M, Morton, J, Sweeney, E, Wilson, L, Brunner, H, Mulliken, J, Wall, SA, Wilkie, A

“…Somatic mosaicism was demonstrated in 6 of 53 informative families, and, of 17 germline mutations in individuals for whom the parental origin of mutation could be demonstrated, 15 arose from the father. …”

Gonadal mosaicism and non-invasive prenatal diagnosis for "reassurance" in sporadic paternal age effect (PAE) disorders by Goriely, A, Wilkie, A

A recurrent mosaic mutation of SMO, encoding the hedgehog signal transducer Smoothened, is the major cause of Curry-Jones syndrome by Twigg, S, Wilkie, A, Hufnagel, R, Miller, K, Zhou, Y, McGowan, S, Taylor, J, Craft, J, Taylor, J, Santoro, S, Huang, T, Hopkin, R, Brady, A, Clayton-Smith, J, Clericuzio, C, Grange, D, Groesser, L, Hafner, C, Horn, D, Temple, I, Dobyns, W, Curry, C, Jones, M, Wilkie, A

“…The combination of asymmetric clinical features, patchy skin manifestations and neoplastic association previously led to the suggestion that this could be a mosaic condition, possibly involving Hedgehog (Hh) signaling. …”

Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism. by Ansari, M, Poke, G, Ferry, Q, Williamson, K, Aldridge, R, Meynert, A, Bengani, H, Chan, C, Kayserili, H, Avci, S, Hennekam, R, Lampe, A, Redeker, E, Homfray, T, Ross, A, Falkenberg Smeland, M, Mansour, S, Parker, M, Cook, J, Splitt, M, Fisher, R, Fryer, A, Magee, A, Wilkie, A, Barnicoat, A

“…Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. …”

Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism by Ansari, M, Poke, G, Ferry, Q, Williamson, K, Aldridge, R, Meynert, A, Bengani, H, Chan, C, Kayserili, H, Avci, Ş, Hennekam, R, Lampe, A, Redeker, E, Homfray, T, Ross, A, Smeland, M, Mansour, S, Parker, M, Cook, J, Splitt, M, Fisher, R, Fryer, A, Magee, A, Wilkie, A, Barnicoat, A

“…Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. …”

Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes. by Twigg, SR, Babbs, C, van den Elzen, M, Goriely, A, Taylor, S, McGowan, S, Giannoulatou, E, Lonie, L, Ragoussis, J, Sadighi Akha, E, Knight, S, Zechi-Ceide, R, Hoogeboom, J, Pober, B, Toriello, H, Wall, SA, Rita Passos-Bueno, M, Brunner, H, Mathijssen, I, Wilkie, A

“…We hypothesized that such individuals might be mosaic for EFNB1 mutations and investigated this possibility in multiple tissue samples from six sporadically presenting males. …”

Germline and somatic mosaicism for FGFR2 mutation in the mother of a child with Crouzon syndrome: Implications for genetic testing in "paternal age-effect" syndromes. by Goriely, A, Lord, H, Lim, J, Johnson, D, Lester, T, Firth, H, Wilkie, A

“…Levels of maternal somatic mosaicism for this mutation, estimated by pyrosequencing, ranged from 3.3% in hair roots to 14.1% in blood. …”

Gastrointestinal disorders in Curry-Jones syndrome: clinical and molecular insights from an affected newborn by Wigby, K, Twigg, S, Broderick, R, Davenport, K, Wilkie, A, Bickler, S, Jones, M

“…<p>Curry-Jones syndrome (CJS) is a pattern of malformation that includes craniosynostosis, pre-axial polysyndactyly, agenesis of the corpus callosum, cutaneous and gastrointestinal abnormalities. A recurrent, mosaic mutation of SMO (c.1234 C&gt;T; p.Leu412Phe) causes CJS. …”

De novo SOX6 variants cause a neurodevelopmental syndrome associated with attention deficit/hyperactivity disorder, craniosynostosis and osteochondroma by Tolchin, D, Yeager, JP, Prasad, P, Calpena, E, Melistaccio, G, Wilkie, A, Et al.

“…Fourteen are&nbsp;<em>de novo</em>, one is inherited from a mosaic father, and four offspring from two families have a paternally inherited variant. …”

Etiological heterogeneity and clinical characteristics of metopic synostosis: Evidence from a tertiary craniofacial unit. by Kini, U, Hurst, J, Byren, J, Wall, SA, Johnson, D, Wilkie, A

“…Chromosomal abnormalities were noted in 8/38 (21.4%) children: mosaic marker chromosome 2, 9p deletion (2/8), 11q deletion, 12pter deletion and duplication of 15q25 with other additional chromosomal abnormalities (3/8). …”

Selfish spermatogonial selection: evidence from an immunohistochemical screen in testes of elderly men by Lim, J, Maher, G, Turner, G, Dudka-Ruszkowska, W, Taylor, S, Rajpert-De Meyts, E, Goriely, A, Wilkie, A

“…These studies imply that normal testes are mosaic for clusters of mutant cells: these clusters are predicted to have altered growth and signalling properties leading to their clonal expansion (selfish spermatogonial selection), but DNA extraction eliminates the possibility to study such processes at a tissue level. …”

Implementation of a genomic medicine multi-disciplinary team approach for rare disease in the clinical setting: a prospective exome sequencing case series by Taylor, J, Craft, J, Blair, E, Wordsworth, S, Beeson, D, Chandratre, S, Cossins, J, Lester, T, Németh, A, Ormondroyd, E, Patel, S, Pagnamenta, A, Taylor, J, Thomson, K, Watkins, H, Wilkie, A, Knight, J

“…Examples were also found where findings from initial genetic testing were reconsidered in the light of exome sequencing including TP63 and PRKAG2 (detection of a partial exon deletion and a mosaic missense pathogenic variant respectively); together with tissue-specific mosaicism involving a cytogenetic abnormality following a normal prenatal array comparative genomic hybridization.…”

Genetic aspects of birth defects: new understandings of old problems. by Prescott, K, Wilkie, A

“…This review describes the importance of genome architecture, parent of origin effects (imprinting), molecular pathophysiology, developmental pathways, mosaicism and cancer predisposition syndromes in the understanding of birth defects. …”

Genetic aspects of birth defects: New understandings of old problems by Prescott, K, Wilkie, A

“…This review describes the importance of genome architecture, parent of origin effects (imprinting), molecular pathophysiology, developmental pathways, mosaicism and cancer predisposition syndromes in the understanding of birth defects. …”

Duplication of the EFNB1 gene in familial hypertelorism: imbalance in ephrin-B1 expression and abnormal phenotypes in humans and mice. by Babbs, C, Stewart, H, Williams, L, Connell, L, Goriely, A, Twigg, SR, Smith, K, Lester, T, Wilkie, A

“…Hence, we propose that X-linked cases resembling Teebi hypertelorism may have a similar mechanism to CFNS, and that cellular mosaicism for different levels of ephrin-B1 (as well as simple presence/absence) leads to craniofacial abnormalities.…”

De novo and rare inherited mutations implicate the transcriptional coregulator TCF20/SPBP in autism spectrum disorder. by Babbs, C, Lloyd, D, Pagnamenta, A, Twigg, SR, Green, J, McGowan, S, Mirza, G, Naples, R, Sharma, V, Volpi, E, Buckle, V, Wall, SA, Knight, S, Parr, JR, Wilkie, A

“…By clinical cytogenetic testing, we identified a family in which two brothers had ASD, mild intellectual disability and a chromosome 22 pericentric inversion, not detected in either parent, indicating de novo mutation with parental germinal mosaicism. We hypothesised that the rearrangement was causative of their ASD and localised the chromosome 22 breakpoints. …”

Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes by Maher, G, Ralph, H, Ding, Z, Koelling, N, Mlcochova, H, Giannoulatou, E, Dhami, P, Paul, D, Stricker, S, Beck, S, McVean, G, Wilkie, A, Goriely, A

“…Mosaic mutations present in the germline have important implications for reproductive risk and disease transmission. …”