gms | German Medical Science

14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT)

17.06. - 21.06.2019, Berlin

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Mutational spectrum and targeted therapy for isolated macrodactyly

Meeting Abstract

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  • presenting/speaker Hengqing Cui - Shanghai 9th People's Hospital, Shanghai Jiaotong University, Shanghai, China
  • Gang Han - Shanghai 9th People's Hospital, Shanghai Jiaotong University, Shanghai, China
  • Bin Wang - Shanghai 9th People's Hospital, Shanghai Jiaotong University, Shanghai, China

International Federation of Societies for Surgery of the Hand. International Federation of Societies for Hand Therapy. 14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT). Berlin, 17.-21.06.2019. Düsseldorf: German Medical Science GMS Publishing House; 2020. DocIFSSH19-953

doi: 10.3205/19ifssh1268, urn:nbn:de:0183-19ifssh12683

Veröffentlicht: 6. Februar 2020

© 2020 Cui et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Objectives/Interrogation: Macrodactyly is a congenital condition characterized by continuous overgrowth of fingers or toes. It is a symptom of PIK3CA-related overgrowth spectrum (PROS), which is caused by mosaic somatic mutation of PIK3CA gene. This study aimed to reveal the mutational spectrum and the targeted drug sensitivity of isolated macrodactyly.

Methods: We included 52 patients diagnosed with isolated macrodactyly from June 2014 to August 2018 in our hospital. Genomic DNA were prepared from different tissues including adipose, skin, bone, nerve, tendon, and vessel of surgically debulked or amputated macrodactylous digits. All exons of PIK3CA were PCR-amplified and sequenced by Sanger sequencing. Clinical manifestations of the patients were recorded. Adipose-derived stem cells from 9 patients with macrodactyly and 3 patients with polydactyly were isolated and cultured. The half maximal inhibitory concentration (IC 50) of rapamycin and BYL719 for these cells were determined.

Results and Conclusions: PIK3CA mutations were detected in 90.4% (47 in 52) of the patients in our cohort of isolated macrodactyly. These mutations clustered into three hotspots, p.His1047Arg (46.2%, 24/52), p.Glu542Lys (17.3%, 9/52), and p.His1047Leu (9.6%, 5/52), which differed from that was found in PROS. Mutations were detected in all tissue types including adipose, skin, bone, nerve, tendon and vessel, irrespective of the overgrown phenotype. Interestingly, the PIK3CA inhibitor BYL719, but not the mTOR inhibitor rapamycin, displayed lower IC50 for macrodactylous adipose-derived stem cells than normal adipose-derived stem cells, indicating selective inhibition of macrodactylous cells. In conclusion, through investigation of the largest cohort of isolated macrodactyly up to date, we revealed a unique mutational spectrum of this condition that differed from other PROS. Moreover, all tissue types in macrodactylous digit could serve as a DNA source for mutation detection. Finally, BYL719 was a potential selective drug for suppression of the overgrowth of the macrodactylous digit. This study will shed light on genetic diagnosis and targeted therapy for isolated macrodactyly.