RESUMO
Trichorhinophalangeal syndrome type I (TRPSI) is a rare disorder that causes distinctive ectodermal, facial, and skeletal features affecting the hair (tricho-), nose (rhino-), and fingers and toes (phalangeal) and is inherited in an autosomal dominant pattern. TRPSI is caused by loss of function variants in TRPS1, involved in the regulation of chondrocyte and perichondrium development. Pathogenic variants in TRPS1 include missense mutations and deletions with variable breakpoints, with only a single instance of an intragenic duplication reported to date. Here we report an affected individual presenting with a classic TRPSI phenotype who is heterozygous for a de novo intragenic â¼36.3-kbp duplication affecting exons 2-4 of TRPS1 Molecular analysis revealed the duplication to be in direct tandem orientation affecting the splicing of TRPS1 The aberrant transcripts are predicted to produce a truncated TRPS1 missing the nuclear localization signal and the GATA and IKAROS-like zinc-finger domains resulting in functional TRPS1 haploinsufficiency. Our study identifies a novel intragenic tandem duplication of TRPS1 and highlights the importance of molecular characterization of intragenic duplications.
Assuntos
Dedos/anormalidades , Doenças do Cabelo/genética , Síndrome de Langer-Giedion/genética , Nariz/anormalidades , Proteínas Repressoras/genética , Idoso , Criança , Proteínas de Ligação a DNA/genética , Éxons/genética , Família , Feminino , Duplicação Gênica/genética , Doenças do Cabelo/etiologia , Humanos , Síndrome de Langer-Giedion/etiologia , Masculino , Pessoa de Meia-Idade , Mutação , Mutação de Sentido Incorreto/genética , Linhagem , Fenótipo , Splicing de RNA/genética , Proteínas Repressoras/metabolismo , Deleção de Sequência/genética , Fatores de Transcrição/genética , Dedos de Zinco/genéticaRESUMO
Trichorhinophalangeal syndrome type I [OMIM #190350] is an autosomal dominant disorder. Common features are: Slowly growing sparse hair, laterally thin eyebrows, bulbous tip of the nose, long philtrum, thin upper lip, protruding ears. Common skeletal anomalies include shortening of phalanges and metacarpals causing mild to severe brachydactyly, cone shaped epiphyses, hip dysplasia and short stature. Recently many reports have been published on the use of assisted reproductive technology (ART) and the increased risk of congenital major malformations or syndromes. We present a 6 years old Turkish Trichorhinophalangeal syndrome (TRPS) case of a twin pair after in vitro fertilization (IVF). TRPS with IVF pregnancy has not been reported previously. This new case reported herein will contribute to a better understanding whether ART pregnancy increases congenital malformations.
