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Bae J, Choi HS, Park SY, et al. Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with Unclassical Pseudopseudohypoparathyroidism. Endocrinol Metab (Seoul). 2018;33(2):252-259doi: 10.3803/EnM.2018.33.2.252.
Bae, J., Choi, H. S., Park, S. Y., Lee, D. E., & Lee, S. (2018). Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with Unclassical Pseudopseudohypoparathyroidism. Endocrinology and metabolism (Seoul, Korea), 33(2), 252-259. https://doi.org/10.3803/EnM.2018.33.2.252
Bae, Jihong, et al. "Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with Unclassical Pseudopseudohypoparathyroidism." Endocrinology and metabolism (Seoul, Korea) vol. 33,2 (2018): 252-259. doi: https://doi.org/10.3803/EnM.2018.33.2.252
Bae J, Choi HS, Park SY, Lee DE, Lee S. Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with Unclassical Pseudopseudohypoparathyroidism. Endocrinol Metab (Seoul). 2018 Jun;33(2):252-259. doi: 10.3803/EnM.2018.33.2.252. PMID: 29947179; PMCID: PMC6021309.
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Endocrinol Metab (Seoul). 2018 Jun;33(2):252-259. doi: 10.3803/EnM.2018.33.2.252.

Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with Unclassical Pseudopseudohypoparathyroidism.

Endocrinology and metabolism (Seoul, Korea)

Jihong Bae, Hong Seok Choi, So Young Park, Do Eun Lee, Sihoon Lee

Affiliations

  1. Department of Internal Medicine and Laboratory of Genomics and Translational Medicine, Gachon University College of Medicine, Incheon, Korea.
  2. Department of Internal Medicine, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea.
  3. Private Practice, Lafayette, CA, USA.
  4. Department of Internal Medicine and Laboratory of Genomics and Translational Medicine, Gachon University College of Medicine, Incheon, Korea. [email protected].

PMID: 29947179 PMCID: PMC6021309 DOI: 10.3803/EnM.2018.33.2.252

Abstract

BACKGROUND: Autosomal-dominant brachydactyly type E is a congenital abnormality characterized by small hands and feet, which is a consequence of shortened metacarpals and metatarsals. We recently encountered a young gentleman exhibiting shortening of 4th and 5th fingers and toes. Initially, we suspected him having pseudopseudohypoparathyroidism (PPHP) because of normal biochemical parameters, including electrolyte, Ca, P, and parathyroid hormone (PTH) levels; however, his mother and maternal grandmother had the same conditions in their hands and feet. Furthermore, his mother showed normal biochemical parameters. To the best of our knowledge, PPHP is inherited via a mutated paternal allele, owing to the paternal imprinting of GNAS (guanine nucleotide binding protein, alpha stimulating) in the renal proximal tubule. Therefore, we decided to further analyze the genetic background in this family.

METHODS: Whole exome sequencing was performed using genomic DNA from the affected mother, son, and the unaffected father as a negative control.

RESULTS: We selected the intersection between 45,490 variants from the mother and 45,646 variants from the son and excluded 27,512 overlapping variants identified from the father. By excluding homogenous and compound heterozygous variants and removing all previously reported variants, 147 variants were identified to be shared by the mother and son. Variants that had least proximities among species were excluded and finally 23 variants remained.

CONCLUSION: Among them, we identified a defect in parathyroid hormone like hormone (PTHLH), encoding the PTH-related protein, to be disease-causative. Herein, we report a family affected with brachydactyly type E2 caused by a novel PTHLH mutation, which was confused with PPHP with unclassical genetic penetrance.

Copyright © 2018 Korean Endocrine Society.

Keywords: Brachydactyly; Parathyroid hormone like hormone; Parathyroid hormone-related protein; Pseudopseudohypoparathyroidism

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

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