-
Claire A Scott,
Vincent Plagnol,
Daniela Nitoiu,
Philip J Bland,
Diana C Blaydon,
Catherine M Chronnell,
Daniel S Poon,
David Bourn,
László Gárdos,
Andrea Császár, [......],
Malcolm Rustin,
Nigel P Burrows,
Chris Bennett,
John I Harper,
Bernard Conrad,
Ishwar C Verma,
Saleem M Taibjee, Celia Moss,
Edel A O'Toole,
David P Kelsell
Journal of Investigative Dermatology 09/2012; · 6.31 Impact Factor
-
Journal of Investigative Dermatology 11/2011; 132(3 Pt 1):730-2. · 6.31 Impact Factor
-
Shefali Rajpopat, Celia Moss,
Jemima Mellerio,
Anders Vahlquist,
Agneta Gånemo,
Maritta Hellstrom-Pigg,
Andrew Ilchyshyn,
Nigel Burrows,
Giles Lestringant,
Aileen Taylor, [......],
Philip Fleckman,
David Everman,
Mohamad Fouani,
Hulya Kayserili,
Diana Purvis,
Emma Hobson,
Carol Chu,
Charles Mein,
David Kelsell,
Edel O'Toole
[show abstract]
[hide abstract]
ABSTRACT: To assess the clinical outcomes of 45 cases of harlequin ichthyosis and review the underlying ABCA12 gene mutations in these patients.
Multicenter, retrospective, questionnaire-based survey.
Dermatology research institute.
Patients with harlequin ichthyosis for whom we had performed ABCA12 mutation analysis.
Referring physicians were asked to complete a questionnaire using the patients' notes, detailing the clinical outcome of the affected child. In each case, the causative ABCA12 mutation was identified using standard polymerase chain reaction and sequencing techniques.
Of the 45 cases, the ages of the survivors ranged from 10 months to 25 years, with an overall survival rate of 56%. Death usually occurred in the first 3 months and was attributed to sepsis and/or respiratory failure in 75% of cases. The early introduction of oral retinoids may improve survival, since 83% of those treated survived, whereas 76% who were not given retinoids died. Recurrent skin infections in infancy affected one-third of patients. Problems maintaining weight affected 44%. Three children developed an inflammatory arthritis, and developmental delay was reported in 32%. Mutation analysis revealed that 52% of survivors had compound heterozygous mutations, whereas all deaths were associated with homozygous mutations.
Harlequin ichthyosis should be regarded as a severe chronic disease that is not invariably fatal. With improved neonatal care and probably the early introduction of oral retinoids, the number of survivors is increasing. Compound heterozygotes appear to have a survival advantage.
Archives of dermatology 02/2011; 147(6):681-6. · 4.76 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Autosomal dominant and recessive forms of dystrophic epidermolysis bullosa (DEB) result from mutations in the type VII collagen gene (COL7A1). Although paradigms have emerged for genotype/phenotype correlation in DEB, some pathogenic mutations in COL7A1, notably glycine substitutions within the type VII collagen triple helix, may lead to diagnostic difficulties, since certain glycine substitutions can result in either dominant or recessive mutant alleles. Delineation of glycine substitution mutations into two discrete groups, however, is made difficult by observations that, for some particular glycine substitutions in type VII collagen, the same mutation can result in both dominant and recessive disease. In this report we describe four further glycine missense mutations: p.Gly1483Asp, p.Gly1770Ser, p.Gly2213Arg and p.Gly2369Ser, which can lead to either dominant or recessive DEB, and which result in a spectrum of clinical abnormalities. We also identify a further 30 new glycine substitution mutations that cause either dominant or recessive DEB, but not both. In screening the COL7A1 gene for mutations in individuals with DEB our data highlight that delineation of glycine substitutions in type VII collagen has important implications for genetic counselling.
Acta Dermato-Venereologica 02/2011; 91(3):262-6.
-
Acta Dermato Venereologica 01/2011; 91(3):262-266. · 3.18 Impact Factor
-
Celia Moss
[show abstract]
[hide abstract]
ABSTRACT: Genetic disorders with skin manifestations often affect other organs as well, and diseases with a similar array of features might be linked pathogenetically. Classifying disorders by individual phenotypic components may reveal clusters with a common genetic cause and elucidate pathogenic links. If components are categorized inadequately, however, the method will simply confirm what is known, obscure true links, and suggest false ones.
Journal of Investigative Dermatology 11/2009; 129(11):2543-5. · 6.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent high-profile cases have made paediatricians very aware of the serious implications of either missing or wrongly diagnosing non-accidental injury. Subdural fluid collections in non-mobile infants usually represent haemorrhage caused by non-accidental injury. We report a 6-month-old male who presented to the Accident and Emergency Department of Birmingham Heartlands Hospital with bilateral subdural fluid collections and skin ulcers resembling cigarette burns. Non-accidental injury was considered to be the most likely diagnosis. However, while under observation in hospital, the child's neurological condition deteriorated with progressive cerebral infarctions, and serial photographs of the skin lesions showed failure to heal. The revised diagnosis, confirmed histologically, was Degos disease, an extremely rare and often fatal occlusive vasculopathy. The child was treated palliatively and died 8 weeks after presentation. This report informs doctors of a new simulator of non-accidental injury to be considered in infants with otherwise unexplained subdural fluid collections.
Developmental Medicine & Child Neurology 07/2009; 51(8):647-50. · 2.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We describe two adolescents who presented with end-stage renal failure and clinical features suggestive of Sjögren's syndrome (SS). They both demonstrated severe, chronic, tubulointerstitial inflammation on renal biopsy, high-titre antinuclear antibodies, high immunoglobulin A and G concentrations, positive anti-SSA and anti-SSB antibodies, and negative anti-double-stranded DNA antibodies. One had subjective and objective evidence of the sicca complex (dry eyes and/or dry mouth) and fulfilled the commonly accepted SS consensus criteria. The other showed no evidence of the sicca complex but fulfilled modified criteria for juvenile SS. SS may be underrecognised as a cause of end-stage renal failure in childhood.
Pediatric Nephrology 11/2007; 22(10):1793-7. · 2.52 Impact Factor
-
Diana C Blaydon,
Yoshiyuki Ishii,
Edel A O'Toole,
Harriet C Unsworth,
Muy-Teck Teh,
Franz Rüschendorf,
Claire Sinclair,
Väinö K Hopsu-Havu,
Nicholas Tidman, Celia Moss,
Rosemarie Watson,
David de Berker,
Muhammad Wajid,
Angela M Christiano,
David P Kelsell
[show abstract]
[hide abstract]
ABSTRACT: Anonychia and hyponychia congenita (OMIM 206800) are rare autosomal recessive conditions in which the only presenting phenotype is the absence or severe hypoplasia of all fingernails and toenails. After determining linkage to chromosome 20p13, we identified homozygous or compound heterozygous mutations in the gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, in eight affected families. Rspo4 expression was specifically localized to developing mouse nail mesenchyme at embryonic day 15.5, suggesting a crucial role in nail morphogenesis.
Nature Genetics 12/2006; 38(11):1245-7. · 35.53 Impact Factor
-
Mitsuo Fujimoto,
Suzanne N Leech,
Therina Theron,
Masato Mori,
Heather Fawcett,
Elena Botta,
Yasuyuki Nozaki,
Takanori Yamagata,
Shin-Ichi Moriwaki,
Miria Stefanini,
Mariko Y Momoi,
Hidemi Nakagawa,
Sam Shuster, Celia Moss,
Alan R Lehmann
[show abstract]
[hide abstract]
ABSTRACT: Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are both rare autosomal recessive disorders with defects in DNA repair. They are usually distinct both clinically and genetically but in rare cases, patients exhibit the clinical characteristics of both diseases concurrently. We report two new phenotypically distinct cases of XP with additional features of CS (xeroderma pigmentosum and Cockayne syndrome crossover syndrome (XP/CS)) carrying an identical mutation (G47R) in the XPD gene within the N terminus of the protein. Both patients had clinical features of XP and CS but only one fulfilled most criteria for diagnosing CS. Unusually, patient 1 developed early skin cancer, in contrast to patient 2, who never developed any malignancies. Cells from both these patients have repair defects typical of xeroderma pigmentosum complementation group D (XPD) cells, but also had the phenotype of uncontrolled DNA breakage found specifically in XPD/CS cells and similarly reduced levels of TFIIH. Despite these similarities between our two patients, their clinical features are quite different and the clinical severity correlates with other cellular responses to ultraviolet irradiation.
Journal of Investigative Dermatology 08/2005; 125(1):86-92. · 6.31 Impact Factor
-
David P Kelsell,
Elizabeth E Norgett,
Harriet Unsworth,
Muy-Teck Teh,
Thomas Cullup,
Charles A Mein,
Patricia J Dopping-Hepenstal,
Beverly A Dale,
Gianluca Tadini,
Philip Fleckman, [......],
Andrew Ilchyshyn,
Cameron T Kennedy,
Helen Goodyear, Celia Moss,
David Paige,
John I Harper,
Bryan D Young,
Irene M Leigh,
Robin A J Eady,
Edel A O'Toole
[show abstract]
[hide abstract]
ABSTRACT: Harlequin ichthyosis (HI) is the most severe and frequently lethal form of recessive congenital ichthyosis. Although defects in lipid transport, protein phosphatase activity, and differentiation have been described, the genetic basis underlying the clinical and cellular phenotypes of HI has yet to be determined. By use of single-nucleotide-polymorphism chip technology and homozygosity mapping, a common region of homozygosity was observed in five patients with HI in the chromosomal region 2q35. Sequencing of the ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI. Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder. This finding paves the way for early prenatal diagnosis. In addition, functional studies of ABCA12 will lead to a better understanding of epidermal differentiation and barrier formation.
The American Journal of Human Genetics 06/2005; 76(5):794-803. · 10.60 Impact Factor
-
Journal of Investigative Dermatology 10/2004; 123(3):607-10. · 6.31 Impact Factor
-
Gabrielle H S Ashton,
W H Irwin McLean,
Andrew P South,
Noritaka Oyama,
Frances J D Smith,
Raouf Al-Suwaid,
Abla Al-Ismaily,
David J Atherton,
Catherine A Harwood,
Irene M Leigh, Celia Moss,
Biagio Didona,
Giovanna Zambruno,
Annalisa Patrizi,
Robin A J Eady,
John A McGrath
[show abstract]
[hide abstract]
ABSTRACT: Kindler syndrome (OMIM 173650) is a rare autosomal recessive disorder characterized by trauma-induced blister formation (especially in childhood) and photosensitivity. Other features include mucocutaneous scarring and progressive poikiloderma. There is also an increased risk of skin and mucous membrane malignancy. The disorder was recently mapped to 20p12.3 and pathogenic mutations were identified in a new gene, KIND1. This gene encodes a 677 amino acid protein, kindlin-1, a component of focal contacts in keratinocytes. In this study, we identified four new recurrent mutations in KIND1 in 16 individuals with Kindler syndrome from 13 families of Pakistani (676insC), UK Caucasian (E304X), Omani (W616X), or Italian (958-1G > A) origins. Haplotype analysis demonstrated common ancestral mutant alleles for each mutation, apart from one of the six Pakistani families in which the mutation 676insC (which occurs in a repeat of seven cytosines) was present on a different genetic background. All mutations were homozygous, apart from the three UK Caucasian cases that were all compound heterozygotes (second allele mutations: L302X, 1161delA, 1909delA). All mutations were associated with markedly reduced or absent skin immunostaining with an antikindlin-1 antibody. These loss-of-function KIND1 mutations demonstrate the importance of kindlin-1 in maintaining epithelial integrity, although the mechanism linking this mutant protein to photosensitivity and poikiloderma remains to be determined. Delineation of these recurrent mutations is also relevant to optimizing mutation detection strategies in Kindler syndrome patients from particular ethnic backgrounds.
Journal of Investigative Dermatology 02/2004; 122(1):78-83. · 6.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The inhibitory effect of PUVA on delayed cutaneous hypersensitivity to 2,4-dinitrochloroben-zene (DNCB) has been analysed by sensitizing and challenging patients with psoriasis on shielded and treated areas of skin, and comparing the results with those for untreated patients. PUVA suppresses both induction and expression of delayed cutaneous hypersensitivity by systemic as well as local actions, but the major effect is local inhibition of induction. The possible contributions of Langerhans cell depletion, impaired lymphocyte reactivity, and reduced cutaneous inflammatory responses are discussed.
British Journal of Dermatology 10/1982; 107(5):511 - 516. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cell mediated immune reactivity was studied in eighty-five psoriasis patients and twenty-five healthy controls by an improved (quantitative) method for measuring contact hypersensitivity to 2,4 dinitrochlorobenzene (DNCB). Patients were sensitized with 500 μg DNCB, the lowest dose found to sensitize all healthy subjects. Responses to epicutaneous challenge with a series of concentrations of DNCB were measured as volumes calculated from diameter and thickness and the various groups were compared by the differences in the log dose-response curves. Patients with untreated psoriasis were less responsive than healthy controls; responses were less still in patients treated with dithranol/UV-B/tar and they were least of all in patients treated with photochemotherapy with 8-methoxypsoralen and UV-A (PUVA), particularly in those who pigmented least. Sensitization and challenge at different stages of treatment showed that both induction and elicitation of sensitization were impaired by PUVA. The possible relationship of these changes to DNCB metabolism, Langerhans cell damage and a decrease in circulating T cells is discussed. Although the clinical significance of the findings is unknown, treatment with dithranol/UV-B/tar has proved safe over many years of use.
British Journal of Dermatology 10/1981; 105(5):503 - 508. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Patients receiving photochemotherapy (PUVA) for psoriasis were shown to have an increase in scrum 25-OH vitamin D. The effect was not seen with UV-A alone or 8-MOP alone.
British Journal of Dermatology 09/1981; 105(4):421 - 424. · 3.67 Impact Factor
-
-
[show abstract]
[hide abstract]
ABSTRACT: Mutations in the three genes (LAMA3, LAMB3, and LAMC2) that encode the three chaises (α3, β3, and γ2, respectively) of laminin 5, a protein involved in epidermal-dermal adhesion, have been established as the genetic basis for the inherited blistering skin disorder, Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a child with H-JEB and identified a nonsense mutation in the α3 chain gene (LAMA3) consisting of a homozygous C-to-T transition resulting in a premature termination codon (CGA → TGA) on both alleles. The parents were shown to be heterozygous carriers of the same mutation. Direct mutation analysis was used to perform DNA-based prenatal diagnosis from a chorionic villus biopsy at 10 weeks' gestation in a subsequent pregnancy. The fetus was predicted to be genotypically normal with respect to the LAMA3 mutation.
Genomics.
