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Master Thesis

Caractérisation clinique et moléculaire d'un nouveau syndrome causé par des mutations du gène PITX1

Abstract : PITX1 (OMIM 602149) is a transcription factor essential for hindlimb morphogenesis. Two PITX1-related human disorders have been reported : the Liebenberg syndrome characterized by a partial “arm-to-leg transformation” (due to PITX1 ectopic expression) and a syndromic picture including clubfoot, the possible presence of right tibial hemimelia and preaxial polydactyly (due to PITX1 deletions or mutation).
OBJECTIVE: To report the clinical and molecular characterization of a novel syndrome due to PITX1 mutations.
RESULTS: Patient 1 presented with micrognathia, knee flessum deformity, short stature and urogenital anomalies. His mother (patient 2) showed similar skeletal abnormalities. Patient 3 presented Pierre-Robin sequence, severe knee flessum deformity and genital abnormalities. Radiological features for all of them included mandibular hypoplasia, patellar hypo/aplasia and pelvis abnormalities. Whole exome sequencing detected the PITX1 heterozygous missense mutations c.793G>T in patient 1 and 2 and c.412A>C in patient 3.
DISCUSSION: The patients here reported show a novel distinct recognizable syndrome including first branchial arch, patellar and pelvic developmental abnormalities, possibly associated with short stature and male genital anomalies. Interestingly, the Pitx1-/- mouse model shows a similar phenotype. This condition could be named Mandibular-Pelvic-Patellar syndrome.
MPP syndrome show a partial phenotypic overlap with the Small patella syndrome (TBX4) and the Camptomelic dysplasia (SOX9). Our study expands the spectrum of PITX1-related syndromes and suggests a common pattern of developmental abnormalities in disorders of the PITX1-TBX4-SOX9 signaling pathway.
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Master Thesis
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Submitted on : Tuesday, December 3, 2019 - 5:39:10 PM
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  • HAL Id : dumas-02391941, version 1


Godelieve Morel. Caractérisation clinique et moléculaire d'un nouveau syndrome causé par des mutations du gène PITX1. Médecine humaine et pathologie. 2019. ⟨dumas-02391941⟩



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