Severe brachydactyly and short stature resulting from a novel pathogenic TRPS1 variant within the GATA DNA-binding domain.
Bone
; 123: 153-158, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30914275
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Variação Genética
/
Proteínas de Ligação a DNA
/
Nanismo
/
Fatores de Transcrição GATA
/
Braquidactilia
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Female
/
Humans
Idioma:
En
Revista:
Bone
Assunto da revista:
METABOLISMO
/
ORTOPEDIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Turquia