Mandibular-pelvic-patellar syndrome (mpp) is a novel pitx1-related disorder due to alteration of pitx1 transactivation ability - Université de Lille Accéder directement au contenu
Article Dans Une Revue Human Mutation Année : 2020

Mandibular-pelvic-patellar syndrome (mpp) is a novel pitx1-related disorder due to alteration of pitx1 transactivation ability

Gaetan Lesca

Résumé

PITX1 is a homeobox transcription factor essential for hindlimb morphogenesis. Two PITX1-related human disorders have been reported to date: PITX1 ectopic expression causes Liebenberg syndrome, characterized by malformation of upper limbs showing a "lower limb" appearance; PITX1 deletions or missense variation cause a syndromic picture including clubfoot, tibial hemimelia, and preaxial polydactyly. We report two novel PITX1 missense variants, altering PITX1 transactivation ability, in three individuals from two unrelated families showing a distinct recognizable autosomal dominant syndrome, including first branchial arch, pelvic, patellar, and male genital abnormalities. This syndrome shows striking similarities with the Pitx1-/- mouse model. A partial phenotypic overlap is also observed with Ischiocoxopodopatellar syndrome caused by TBX4 haploinsufficiency, and with the phenotypic spectrum caused by SOX9 anomalies, both genes being PITX1 downstream targets. Our study findings expand the spectrum of PITX1-related disorders and suggest a common pattern of developmental abnormalities in disorders of the PITX1-TBX4-SOX9 signaling pathway.

Dates et versions

hal-03405413 , version 1 (27-10-2021)

Identifiants

Citer

Godelieve Morel, Celine Duhamel, Simon Boussion, Frederic Frenois, Gaetan Lesca, et al.. Mandibular-pelvic-patellar syndrome (mpp) is a novel pitx1-related disorder due to alteration of pitx1 transactivation ability. Human Mutation, 2020, Human mutation, 41 (9), pp.1499-1506. ⟨10.1002/humu.24070⟩. ⟨hal-03405413⟩
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