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New insight into clinical heterogeneity and inheritance diversity of FBLN5-related cutis laxa.
Gharesouran, Jalal; Hosseinzadeh, Hassan; Ghafouri-Fard, Soudeh; Jabbari Moghadam, Yalda; Ahmadian Heris, Javad; Jafari-Rouhi, Amir Hossein; Taheri, Mohammad; Rezazadeh, Maryam.
Afiliación
  • Gharesouran J; Molecular Genetics Division, GMG Center, Tabriz, Iran.
  • Hosseinzadeh H; Division of Medical Genetics, Tabriz Children's Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Ghafouri-Fard S; Molecular Genetics Division, GMG Center, Tabriz, Iran.
  • Jabbari Moghadam Y; Division of Medical Genetics, Tabriz Children's Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Ahmadian Heris J; Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Jafari-Rouhi AH; Department of Otorhinolaryngology, School of Medicine, Sina Medical Research and Training Hospital, Children Medical Research and Training Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Taheri M; Department of Pediatrics, School of Medicine, Children Medical Research and Training Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Rezazadeh M; Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Orphanet J Rare Dis ; 16(1): 51, 2021 01 28.
Article en En | MEDLINE | ID: mdl-33509220
BACKGROUND: FBLN5-related cutis laxa (CL) is a rare disorder that involves elastic fiber-enriched tissues and is characterized by lax skin and variable systemic involvement such as pulmonary emphysema, arterial involvement, inguinal hernias, hollow viscus diverticula and pyloric stenosis. This type of CL follows mostly autosomal recessive (AR) and less commonly autosomal dominant patterns of inheritance. RESULTS: In this study, we detected a novel homozygous missense variant in exon 6 of FBLN5 gene (c.G544C, p.A182P) by using whole exome sequencing in a consanguineous Iranian family with two affected members. Our twin patients showed some of the clinical manifestation of FBLN5-related CL but they did not present pulmonary complications, gastrointestinal and genitourinary abnormalities. The notable thing about this monozygotic twin sisters is that only one of them showed ventricular septal defect, suggesting that this type of CL has intrafamilial variability. Co-segregation analysis showed the patients' parents and relatives were heterozygous for detected variation suggesting AR form of the CL. In silico prediction tools showed that this mutation is pathogenic and 3D modeling of the normal and mutant protein revealed relative structural alteration of fibulin-5 suggesting that the A182P can contribute to the CL phenotype via the combined effect of lack of protein function and partly misfolding-associated toxicity. CONCLUSION: We underlined the probable roles and functions of the involved domain of fibulin-5 and proposed some possible mechanisms involved in AR form of FBLN5-related CL. However, further functional studies and subsequent clinical and molecular investigations are needed to confirm our findings.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de la Matriz Extracelular / Cutis Laxo Tipo de estudio: Prognostic_studies Límite: Female / Humans País/Región como asunto: Asia Idioma: En Revista: Orphanet J Rare Dis Asunto de la revista: MEDICINA Año: 2021 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de la Matriz Extracelular / Cutis Laxo Tipo de estudio: Prognostic_studies Límite: Female / Humans País/Región como asunto: Asia Idioma: En Revista: Orphanet J Rare Dis Asunto de la revista: MEDICINA Año: 2021 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Reino Unido