Clinical spectrum of females with HCCS mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (MLS) syndrome
| العنوان: | Clinical spectrum of females with HCCS mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (MLS) syndrome |
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| المؤلفون: | Christiane Zweier, Madeleine Joubert, Ute Moog, Isabella Rau, Sigrid Fuchs, Hiram Larangeira de Almeida, Bertrand Isidor, Augusta M. A. Lachmeijer, Helen Fryssira, Vanessa A. van Rahden, Anna Jauch, Friederike K Kosyna, Kerstin Kutsche |
| المساهمون: | Institute of Human Genetics, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Dermatology, Federal and Catholic University of Pelotas, Medical Genetics, 'Aghia Sophia' Children's Hospital, Unité de Génétique Clinique, Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Human Genetics Institute, Heidelberg University, Service de Pathologie, Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Femme-Enfant-Adolescent, Department of Clinical Genetics, VU University Medical Center [Amsterdam], Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), BMC, Ed., Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Hôpital Femme-Enfant-Adolescent-Centre hospitalier universitaire de Nantes (CHU Nantes), Human genetics, EMGO - Quality of care |
| المصدر: | Orphanet Journal of Rare Diseases Orphanet Journal of Rare Diseases, BioMed Central, 2014, 9 (1), pp.53. ⟨10.1186/1750-1172-9-53⟩ Orphanet Journal of Rare Diseases, 9:53. BioMed Central van Rahden, V A, Rau, I, Fuchs, S, Kosyna, F K, de Almeida, H L, Fryssira, H, Isidor, B, Jauch, A, Joubert, M, Lachmeijer, A M A, Zweier, C, Moog, U & Kutsche, K 2014, ' Clinical spectrum of females with HCCS mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (MLS) syndrome ', Orphanet Journal of Rare Diseases, vol. 9, 53 . https://doi.org/10.1186/1750-1172-9-53 |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Microcephaly, Pathology, HCCS, [SDV.GEN] Life Sciences [q-bio]/Genetics, Microphthalmia, 610 Medical sciences Medicine, Linear skin defects, Medizinische Fakultät, Microphthalmos, Genetics(clinical), Pharmacology (medical), Child, Genetics (clinical), X chromosome, Skin, Medicine(all), 0303 health sciences, medicine.diagnostic_test, 030305 genetics & heredity, Genetic Diseases, X-Linked, General Medicine, 3. Good health, Child, Preschool, Female, medicine.medical_specialty, Monosomy, 03 medical and health sciences, Internal medicine, medicine, Humans, ddc:610, Sclerocornea, 030304 developmental biology, X-linked, Chromosomes, Human, X, [SDV.GEN]Life Sciences [q-bio]/Genetics, Anophthalmia, business.industry, Research, Infant, medicine.disease, Endocrinology, Skin Abnormalities, X chromosome inactivation, business, Fluorescence in situ hybridization |
| الوصف: | International audience; BACKGROUND: Segmental Xp22.2 monosomy or a heterozygous HCCS mutation is associated with the microphthalmia with linear skin defects (MLS) or MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome, an X-linked disorder with male lethality. HCCS encodes the holocytochrome c-type synthase involved in mitochondrial oxidative phosphorylation (OXPHOS) and programmed cell death. METHODS: We characterized the X-chromosomal abnormality encompassing HCCS or an intragenic mutation in this gene in six new female patients with an MLS phenotype by cytogenetic analysis, fluorescence in situ hybridization, sequencing, and quantitative real-time PCR. The X chromosome inactivation (XCI) pattern was determined and clinical data of the patients were reviewed. RESULTS: Two terminal Xp deletions of >=11.2 Mb, two submicroscopic copy number losses, one of ~850 kb and one of >=3 Mb, all covering HCCS, 1 nonsense, and one mosaic 2-bp deletion in HCCS are reported. All females had a completely (>98:2) or slightly skewed (82:18) XCI pattern. The most consistent clinical features were microphthalmia/anophthalmia and sclerocornea/corneal opacity in all patients and congenital linear skin defects in 4/6. Additional manifestations included various ocular anomalies, cardiac defects, brain imaging abnormalities, microcephaly, postnatal growth retardation, and facial dysmorphism. However, no obvious clinical sign was observed in three female carriers who were relatives of one patient. CONCLUSION: Our findings showed a wide phenotypic spectrum ranging from asymptomatic females with an HCCS mutation to patients with a neonatal lethal MLS form. Somatic mosaicism and the different ability of embryonic cells to cope with an OXPHOS defect and/or enhanced cell death upon HCCS deficiency likely underlie the great variability in phenotypes. |
| وصف الملف: | application/pdf |
| تدمد: | 1750-1172 |
| DOI: | 10.1186/1750-1172-9-53 |
| DOI: | 10.1186/1750-1172-9-53⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a29f6f7dfe1d0bcd60f948d37a1dff6 https://doi.org/10.1186/1750-1172-9-53 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4a29f6f7dfe1d0bcd60f948d37a1dff6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17501172 |
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| DOI: | 10.1186/1750-1172-9-53 |