Fabry disease due to D313Y and novel GLA mutations
Date
2017Language
en
Keyword
Abstract
Objectives Our aim is to report four novel α-gal A gene (GLA) mutations resulting in Fabry disease (FD) and provide evidence of pathogenicity of the D313Y mutation regarding which contradictory data have been presented in the literature. Setting and participants Twenty-five family members of nine unrelated patients with definite FD diagnosis, 10 clinically suspected cases and 18 members of their families were included in this polycentric cohort study. Primary and secondary outcome measures Genotyping and measurement of lyso-Gb 3 was performed in all individuals. The α-Gal A activity was measured in all men as well as plasma and urine Gb 3 concentration in selected cases. Optical and electron microscopy was performed in kidney biopsies of selected patients. All the above were evaluated in parallel with the clinical data of the patients. Results Fourteen new cases of FD were recognised, four of which were carrying already described GLA mutations. Four novel GLA mutations, namely c.835C>T, c.280T>A, c.924A>C and c.511G>A, resulting in a classic FD phenotype were identified. Moreover, FD was definitely diagnosed in five patients carrying the D313Y mutation. Eight D313Y carriers were presenting signs of FD despite not fulfilling the criteria of the disease, two had no FD signs and two others were apparently healthy. Conclusions Four novel GLA pathogenic mutations are reported and evidence of pathogenicity of the D313Y mutation is provided. It seems that the D313Y mutation is related to a later-onset milder phenotype than the typical phenotype with normal lysoGb 3 concentration. Our study underlines the significance of family member genotyping and newborn screening to avoid misdiagnoses and crucial delays in diagnosis and treatment of the disease. © Article author(s) 2017.
Collections
Related items
Showing items related by title, author, creator and subject.
-
Mutation profile of KRAS and BRAF genes in patients with colorectal cancer: Association with morphological and prognostic criteria
Samara M., Kapatou K., Ioannou M., Kostopoulou Ε., Papamichali R., Papandreou C., Athanasiadis A., Koukoulis G. (2015)KRAS and BRAF mutations are well-recognized molecular alterations during colorectal carcinogenesis, but there is little agreement on their effect on tumor characteristics. Therefore, we aimed to evaluate the distribution ... -
TP53 mutations and protein immunopositivity may predict for poor outcome but also for trastuzumab benefit in patients with early breast cancer treated in the adjuvant setting
Fountzilas G., Giannoulatou E., Alexopoulou Z., Zagouri F., Timotheadou E., Papadopoulou K., Lakis S., Bobos M., Poulios C., Sotiropoulou M., Lyberopoulou A., Gogas H., Pentheroudakis G., Pectasides D., Koutras A., Christodoulou C., Papandreou C., Samantas E., Papakostas P., Kosmidis P., Bafaloukos D., Karanikiotis C., Dimopoulos M.-A., Kotoula V. (2016)Background: We investigated the impact of PIK3CA and TP53 mutations and p53 protein status on the outcome of patients who had been treated with adjuvant anthracycline-taxane chemotherapy within clinical trials in the pre- ... -
AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders
Salpietro V., Dixon C.L., Guo H., Bello O.D., Vandrovcova J., Efthymiou S., Maroofian R., Heimer G., Burglen L., Valence S., Torti E., Hacke M., Rankin J., Tariq H., Colin E., Procaccio V., Striano P., Mankad K., Lieb A., Chen S., Pisani L., Bettencourt C., Männikkö R., Manole A., Brusco A., Grosso E., Ferrero G.B., Armstrong-Moron J., Gueden S., Bar-Yosef O., Tzadok M., Monaghan K.G., Santiago-Sim T., Person R.E., Cho M.T., Willaert R., Yoo Y., Chae J.-H., Quan Y., Wu H., Wang T., Bernier R.A., Xia K., Blesson A., Jain M., Motazacker M.M., Jaeger B., Schneider A.L., Boysen K., Muir A.M., Myers C.T., Gavrilova R.H., Gunderson L., Schultz-Rogers L., Klee E.W., Dyment D., Osmond M., Parellada M., Llorente C., Gonzalez-Peñas J., Carracedo A., Van Haeringen A., Ruivenkamp C., Nava C., Heron D., Nardello R., Iacomino M., Minetti C., Skabar A., Fabretto A., Hanna M.G., Bugiardini E., Hostettler I., O’Callaghan B., Khan A., Cortese A., O’Connor E., Yau W.Y., Bourinaris T., Kaiyrzhanov R., Chelban V., Madej M., Diana M.C., Vari M.S., Pedemonte M., Bruno C., Balagura G., Scala M., Fiorillo C., Nobili L., Malintan N.T., Zanetti M.N., Krishnakumar S.S., Lignani G., Jepson J.E.C., Broda P., Baldassari S., Rossi P., Fruscione F., Madia F., Traverso M., De-Marco P., Pérez-Dueñas B., Munell F., Kriouile Y., El-Khorassani M., Karashova B., Avdjieva D., Kathom H., Tincheva R., Van-Maldergem L., Nachbauer W., Boesch S., Gagliano A., Amadori E., Goraya J.S., Sultan T., Kirmani S., Ibrahim S., Jan F., Mine J., Banu S., Veggiotti P., Zuccotti G.V., Ferrari M.D., Van Den Maagdenberg A.M.J., Verrotti A., Marseglia G.L., Savasta S., Soler M.A., Scuderi C., Borgione E., Chimenz R., Gitto E., Dipasquale V., Sallemi A., Fusco M., Cuppari C., Cutrupi M.C., Ruggieri M., Cama A., Capra V., Mencacci N.E., Boles R., Gupta N., Kabra M., Papacostas S., Zamba-Papanicolaou E., Dardiotis E., Maqbool S., Rana N., Atawneh O., Lim S.Y., Shaikh F., Koutsis G., Breza M., Coviello D.A., Dauvilliers Y.A., AlKhawaja I., AlKhawaja M., Al-Mutairi F., Stojkovic T., Ferrucci V., Zollo M., Alkuraya F.S., Kinali M., Sherifa H., Benrhouma H., Turki I.B.Y., Tazir M., Obeid M., Bakhtadze S., Saadi N.W., Zaki M.S., Triki C.C., Benfenati F., Gustincich S., Kara M., Belcastro V., Specchio N., Capovilla G., Karimiani E.G., Salih A.M., Okubadejo N.U., Ojo O.O., Oshinaike O.O., Oguntunde O., Wahab K., Bello A.H., Abubakar S., Obiabo Y., Nwazor E., Ekenze O., Williams U., Iyagba A., Taiwo L., Komolafe M., Senkevich K., Shashkin C., Zharkynbekova N., Koneyev K., Manizha G., Isrofilov M., Guliyeva U., Salayev K., Khachatryan S., Rossi S., Silvestri G., Haridy N., Ramenghi L.A., Xiromerisiou G., David E., Aguennouz M., Fidani L., Spanaki C., Tucci A., Raspall-Chaure M., Chez M., Tsai A., Fassi E., Shinawi M., Constantino J.N., De Zorzi R., Fortuna S., Kok F., Keren B., Bonneau D., Choi M., Benzeev B., Zara F., Mefford H.C., Scheffer I.E., Clayton-Smith J., Macaya A., Rothman J.E., Eichler E.E., Kullmann D.M., Houlden H., SYNAPS Study Group (2019)AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at ...