J Pediatr Genet 2020; 09(02): 125-131
DOI: 10.1055/s-0039-1698806
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Identification of a Novel 19-bp Deletion Mutation in LTBP4 Using Exome Sequencing in Two Siblings with Autosomal Recessive Cutis Laxa Type 1C

1   Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
Nitika Langeh
1   Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
Aparajit Sridharan
2   Strand Life Sciences, Bangalore, Karnataka, India
Madhulika Kabra
1   Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi, India
› Author Affiliations
Further Information

Publication History

29 May 2019

08 September 2019

Publication Date:
22 October 2019 (online)


Autosomal recessive type I cutis laxa is genetically heterogeneous. Biallelic mutations in latent transforming growth factor β-binding protein 4 (LTBP4; MIM*604710) lead to type 1C cutis laxa due to nonsense, frameshift, single base pair indels, or duplication mutations. In this report, we describe the first Indian family with cutis laxa as a result of a novel 19 base pair homozygous deletion leading to premature termination of short isoform LTBP-4S.

  • References

  • 1 Callewaert B, Su CT, Van Damme T. , et al. Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa. Hum Mutat 2013; 34 (01) 111-121
  • 2 Kantola AK, Ryynänen MJ, Lhota F, Keski-Oja J, Koli K. Independent regulation of short and long forms of latent TGF-β binding protein (LTBP)-4 in cultured fibroblasts and human tissues. J Cell Physiol 2010; 223 (03) 727-736
  • 3 Kantola AK, Keski-Oja J, Koli K. Fibronectin and heparin binding domains of latent TGF-β binding protein (LTBP)-4 mediate matrix targeting and cell adhesion. Exp Cell Res 2008; 314 (13) 2488-2500
  • 4 Mannan AU, Singh J, Lakshmikeshava R. , et al. Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India. J Hum Genet 2016; 61 (06) 515-522
  • 5 Richards S, Aziz N, Bale S. , et al; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (05) 405-424
  • 6 Urban Z, Hucthagowder V, Schürmann N. , et al. Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. Am J Hum Genet 2009; 85 (05) 593-605
  • 7 Su CT, Huang JW, Chiang CK. , et al. Latent transforming growth factor binding protein 4 regulates transforming growth factor beta receptor stability. Hum Mol Genet 2015; 24 (14) 4024-4036
  • 8 Dabovic B, Chen Y, Choi J. , et al. Dual functions for LTBP in lung development: LTBP-4 independently modulates elastogenesis and TGF-β activity. J Cell Physiol 2009; 219 (01) 14-22
  • 9 Sterner-Kock A, Thorey IS, Koli K. , et al. Disruption of the gene encoding the latent transforming growth factor-β binding protein 4 (LTBP-4) causes abnormal lung development, cardiomyopathy, and colorectal cancer. Genes Dev 2002; 16 (17) 2264-2273
  • 10 Bultmann-Mellin I, Essers J, van Heijingen PM, von Melchner H, Sengle G, Sterner-Kock A. Function of Ltbp-4L and fibulin-4 in survival and elastogenesis in mice. Dis Model Mech 2016; 9 (11) 1367-1374
  • 11 Bultmann-Mellin I, Conradi A, Maul AC. , et al. Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct functions for Ltbp-4 isoforms. Dis Model Mech 2015; 8 (04) 403-415