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Whole exome sequencing identified three ABCC6 variants in two Pakistani families with pseudoxanthoma elasticum phenotype

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Abstract

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder of ectopic mineralization and fragmentation of elastic fibers in skin, eyes, cardiovascular and digestive system. PXE is caused by sequence variants in ABCC6, which encodes multidrug resistance-associated protein 6 (MRP6, also known as the ABCC6 protein). MRP6 is an important regulator of inorganic plasma pyrophosphate that acts as an inhibitor of ectopic mineralization observed in PXE patients with low inorganic plasma pyrophosphate levels. The current study was designed to investigate underlying genetic defect in two unrelated Pakistani families affected with PXE. Whole exome sequencing followed by Sanger sequencing was performed to identify causative variants. A novel homozygous frameshift variant (c.1799_1805dupGTCTGGT) was identified in one family and two previously reported missense variants (c.2294G > A and c.2974G > A) in compound heterozygous form in the other family. We identified ABCC6 variants that are likely cause of the PXE disease in the tested families. Genetic analysis of these families could be useful for pre-symptomatic diagnosis and genetic counselling of the affected families.

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Acknowledgements

We are grateful to all patients and their family members who participated in the study. Fehmida F. Khan is supported by Higher Education Commission of Pakistan through Indigenous Ph.D. Fellowship Scheme (PIN: 213-57700-2BM2-049).

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Authors and Affiliations

  1. Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan

    Fehmida Farid Khan & Muhammad Naeem

  2. Department of Dermatology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan

    Muhammad Erfan

  3. Department of Dermatology, Federal Government Services Hospital, Islamabad, Pakistan

    Nigar Kanwal

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  1. Fehmida Farid Khan
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  2. Muhammad Erfan
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  3. Nigar Kanwal
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  4. Muhammad Naeem
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Correspondence to Muhammad Naeem.

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Khan, F.F., Erfan, M., Kanwal, N. et al. Whole exome sequencing identified three ABCC6 variants in two Pakistani families with pseudoxanthoma elasticum phenotype. Mol Biol Rep 46, 1363–1368 (2019). https://doi.org/10.1007/s11033-018-04581-x

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  • DOI: https://doi.org/10.1007/s11033-018-04581-x

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