Oral Free Paper Session: Oral Presentation 8published_or_final_versio

Chan, GCF

Choi, KY

Chow, CP

Chow, W

Chung, BHY

Ip, JKJ

Kuong, EEYL

Leung, GKC

Li, CH

To, MKT

Wong, WL

Yeung, KS

HKU Scholars Hub

Title Mutation in PIK3CA leading to developmental mosaic disordersAuthor(s)Yeung, KS; Leung, GKC; Wong, WL; Li, CH; Choi, KY; Kuong,EEYL; Chow, W; To, MKT; Ip, JKJ; Chow, CP; Chan, GCF;Chung, BHYCitationThe 3rd Annual Scientific Meeting of the Hong Kong College ofPaediatricians (HKCPaed), Hong Kong, China, 5-6 December2015, p. 27Issued Date 2015URL http://hdl.handle.net/10722/222595Rights This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.27ORAL PRESENTATION 8:Mutation in PIK3CA leading to developmental mosaic disordersYeung KS,1 Leung GKC,1 Wong WL,1 Li CH,2 Choi KY,3 Kuong E,4 Chow W,4 To M,4Ip J,5 Chow CP,6 Chan GCF,1 Chung BHY11Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, TheUniversity of Hong Kong; 2Department of Paediatrics & Adolescent Medicine, Tuen MunHospital; 3Department of Orthopaedics & Traumatology, Tuen Mun Hospital; 4Departmentof Orthopaedics & Traumatology, Queen Mary Hospital; 5Department of Radiology, QueenMary Hospital; 6Child Assessment Service, Department of Health, Hong KongBackground and aimsMutation in phosphatidylinositol-4, 5-bisphosphate 3-kinase (PIK3CA), one of the genesinvolved in the PI3K/AKT/mTOR pathway, is associated with developmental mosaicdisorders which are now collectively termed as PIK3CA-Related Overgrowth Spectrum(PROS). PROS can be further divided into two subgroups based on the affected bodysystems, which are body asymmetrical overgrowth and central nervous system (CNS)overgrowth respectively. Body asymmetrical overgrowth includes diseases such asCLOVES Syndrome, Klippel-Trenaunay Syndrome, Cystic Hygroma and FibroadiposeHyperplasia. More than 90% of these patients have somatic mutations in one of the 4mutation hotspots in PIK3CA. CNS overgrowth includes diseases such as MegalencephalyPolymicrogyria Polydactyly Hydrocephalus Syndrome (MPPH) and MegalencephalyCapillary Malformation Syndromes (MCAP). Patients who have CNS overgrowth havemegalencephaly and at the same time developmental delay and/or autistic spectrumdisorder. We have ten patients that are suspected to have PROS, and we aim to identifythe diseasing causing mutation in each patient.MethodsFor patients who have body asymmetrical overgrowth, somatic mutations can only bedetected on affected tissues. Since there are mutation hotspots, digital PCR was used toidentify low level somatic mosaicism. For the 2 patients with CNS overgrowth, mutationcan be detected on blood, saliva and buccal tissues. Whole exome sequencing was usedto identify the diseasing causing mutation.ResultsIn 7 out of 8 patients with asymmetrical overgrowth, somatic mutations in PIK3CA havebeen identified. The percentage of mutant in these patients ranged from 3.3% to 31.6%.For the 2 remaining patients with CNS overgrowth, 1 reported somatic mutation with 4.5%mutant and 1 novel germline mutation in PIK3CA have been identified.ConclusionIn order to obtain a molecular diagnosis of PROS, the correct choices of affected tissues andsequencing technology are important. Surgical debulking is now the only option for treatmentfor PROS. With the identification of mutations in PIK3CA, inhibitors that inhibit PI3K/AKT/mTOR pathway may be used in controlling the progressive overgrowth in patients.AcknowledgementThis work was supported by SK Yee Medical Research Fund and Society for Relief ofDisabled Children.Appendix I(Oral Free Paper Session)

Mutation in PIK3CA leading to developmental mosaic disorders

Mutation in PIK3CA leading to developmental mosaic disorders

Abstract

Similar works

Full text

Available Versions

HKU Scholars Hub