Clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review
Abstract Background Cutis laxa (CL) is a group of rare connective tissue disorders mainly characterized by wrinkled, redundant, inelastic, and sagging skin. Besides skin anomalies, in most CL forms multiple organs are involved, leading to severe multisystem disorders involving skeletal, cardiovascul...
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doaj-83e40b432db64adcb59920b19fd468442020-11-24T21:29:05ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-07-0177n/an/a10.1002/mgg3.735Clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature reviewMarco Ritelli0Francisco Cammarata‐Scalisi1Valeria Cinquina2Marina Colombi3Division of Biology and Genetics, Department of Molecular and Translational Medicine University of Brescia Brescia ItalyUnit of Medical Genetics, Department of Pediatrics, Faculty of Medicine University of the Andes Mérida VenezuelaDivision of Biology and Genetics, Department of Molecular and Translational Medicine University of Brescia Brescia ItalyDivision of Biology and Genetics, Department of Molecular and Translational Medicine University of Brescia Brescia ItalyAbstract Background Cutis laxa (CL) is a group of rare connective tissue disorders mainly characterized by wrinkled, redundant, inelastic, and sagging skin. Besides skin anomalies, in most CL forms multiple organs are involved, leading to severe multisystem disorders involving skeletal, cardiovascular, pulmonary, and central nervous systems. CL might be challenging to diagnose because of its different inheritance patterns, extensive phenotypic variability, and genetic heterogeneity. Herein, we report the clinical and molecular characterization of an 18‐month‐old infant with signs suggestive of recessive cutis laxa type 1C (ARCL1C), although with a relatively mild presentation. Methods To confirm the clinical suspicion, mutational screening of all the exons and intron‐flanking regions of the latent transforming growth factor‐beta binding protein 4 gene (LTBP4) was performed by Sanger sequencing on an ABI3130XL Genetic Analyzer. Results Apart from the presence of the dermatological hallmark, the reported patient did not show pulmonary emphysema, which is the most common and discriminative finding of ARCL1C together with gastrointestinal and urinary involvement. Indeed, pulmonary involvement only included episodes of respiratory distress and diaphragmatic eventration; intestinal dilation and tortuosity and hydronephrosis were also present. Molecular analysis disclosed the novel homozygous c.1450del (p.Arg484Glyfs*290) pathogenic variant in exon 12 of LTBP4, thus leading to the diagnosis of ARCL1C. Conclusion Our findings expand both the knowledge of the clinical phenotype and the allelic repertoire of ARCL1C. The comparison of the patient's features with those of the other patients reported up to now offers future perspectives for clinical research in this field.https://doi.org/10.1002/mgg3.735ARCL1Cautosomal recessive cutis laxa type 1Clatent transforming growth factor‐beta binding protein 4LTBP4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marco Ritelli Francisco Cammarata‐Scalisi Valeria Cinquina Marina Colombi |
spellingShingle |
Marco Ritelli Francisco Cammarata‐Scalisi Valeria Cinquina Marina Colombi Clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review Molecular Genetics & Genomic Medicine ARCL1C autosomal recessive cutis laxa type 1C latent transforming growth factor‐beta binding protein 4 LTBP4 |
author_facet |
Marco Ritelli Francisco Cammarata‐Scalisi Valeria Cinquina Marina Colombi |
author_sort |
Marco Ritelli |
title |
Clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review |
title_short |
Clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review |
title_full |
Clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review |
title_fullStr |
Clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review |
title_full_unstemmed |
Clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review |
title_sort |
clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1c due to a novel ltbp4 pathogenic variant, and literature review |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2019-07-01 |
description |
Abstract Background Cutis laxa (CL) is a group of rare connective tissue disorders mainly characterized by wrinkled, redundant, inelastic, and sagging skin. Besides skin anomalies, in most CL forms multiple organs are involved, leading to severe multisystem disorders involving skeletal, cardiovascular, pulmonary, and central nervous systems. CL might be challenging to diagnose because of its different inheritance patterns, extensive phenotypic variability, and genetic heterogeneity. Herein, we report the clinical and molecular characterization of an 18‐month‐old infant with signs suggestive of recessive cutis laxa type 1C (ARCL1C), although with a relatively mild presentation. Methods To confirm the clinical suspicion, mutational screening of all the exons and intron‐flanking regions of the latent transforming growth factor‐beta binding protein 4 gene (LTBP4) was performed by Sanger sequencing on an ABI3130XL Genetic Analyzer. Results Apart from the presence of the dermatological hallmark, the reported patient did not show pulmonary emphysema, which is the most common and discriminative finding of ARCL1C together with gastrointestinal and urinary involvement. Indeed, pulmonary involvement only included episodes of respiratory distress and diaphragmatic eventration; intestinal dilation and tortuosity and hydronephrosis were also present. Molecular analysis disclosed the novel homozygous c.1450del (p.Arg484Glyfs*290) pathogenic variant in exon 12 of LTBP4, thus leading to the diagnosis of ARCL1C. Conclusion Our findings expand both the knowledge of the clinical phenotype and the allelic repertoire of ARCL1C. The comparison of the patient's features with those of the other patients reported up to now offers future perspectives for clinical research in this field. |
topic |
ARCL1C autosomal recessive cutis laxa type 1C latent transforming growth factor‐beta binding protein 4 LTBP4 |
url |
https://doi.org/10.1002/mgg3.735 |
work_keys_str_mv |
AT marcoritelli clinicalandmolecularcharacterizationofan18montholdinfantwithautosomalrecessivecutislaxatype1cduetoanovelltbp4pathogenicvariantandliteraturereview AT franciscocammaratascalisi clinicalandmolecularcharacterizationofan18montholdinfantwithautosomalrecessivecutislaxatype1cduetoanovelltbp4pathogenicvariantandliteraturereview AT valeriacinquina clinicalandmolecularcharacterizationofan18montholdinfantwithautosomalrecessivecutislaxatype1cduetoanovelltbp4pathogenicvariantandliteraturereview AT marinacolombi clinicalandmolecularcharacterizationofan18montholdinfantwithautosomalrecessivecutislaxatype1cduetoanovelltbp4pathogenicvariantandliteraturereview |
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