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Severe brachydactyly and short stature resulting from a novel pathogenic TRPS1 variant within the GATA DNA-binding domain.

Authors :
Karaca A
Reyes M
Shumate LT
Taskaldiran I
Omma T
Ersoz Gulcelik N
Bastepe M
Source :
Bone [Bone] 2019 Jun; Vol. 123, pp. 153-158. Date of Electronic Publication: 2019 Mar 23.
Publication Year :
2019

Abstract

Brachydactyly type E, which can be an isolated finding or part of a syndrome in combination with other clinical anomalies, involves metacarpals and metatarsals with or without short phalanges. Herein we report two unrelated Turkish females who presented with brachydactyly type E and vitamin D deficiency in the absence of marked alterations in serum calcium, phosphate, and parathyroid hormone. After excluding disease-causing variants in two candidate genes, PTHLH and PDE4D, we identified different pathogenic variants in TRPS1, the gene mutated in patients with tricho-rhino-phalangeal syndrome (TRPS). In one of the patients, who displayed severe brachydactyly and short stature, we identified a novel heterozygous missense pathogenic variant in exon 6 (c.2783A>G, p.Tyr928Cys), located within the GATA DNA-binding domain. The second patient, who had relatively milder brachydactyly and was of normal height, carried a heterozygous nonsense pathogenic variant in exon 4 (c. 1870C>T, p.Arg624Ter), which has been previously described. Both pathogenic variants segregated in affected family members. The patients additionally showed sparse hair and a bulbous nose, consistent with the clinical features of TRPS. Our findings, in addition to identifying the genetic cause of brachydactyly in two unrelated kindreds, emphasize the role of pathogenic TRPS1 variants in the development of brachydactyly type E and highlight the GATA DNA-binding region of TRPS1 protein with respect to phenotype-genotype correlation.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1873-2763
Volume :
123
Database :
MEDLINE
Journal :
Bone
Publication Type :
Academic Journal
Accession number :
30914275
Full Text :
https://doi.org/10.1016/j.bone.2019.03.028