TY - JOUR
T1 - Fragile X syndrome screening in pregnant women and women planning pregnancy shows a remarkably high FMR1 premutation prevalence in the Balearic Islands
AU - Alfaro Arenas, Ramona
AU - Rosell Andreo, Jordi
AU - Heine Suñer, Dami
AU - Pía Cordero, María
AU - Fernández Yagüe, Consuelo
AU - Cerdá, Catalina
AU - Amengual, Jerónima
AU - Lladó, Margalida
AU - de Juan, Elena Pascual
AU - Mariscal, Teresa
AU - López Redondo, Pilar
AU - Román, Olga
AU - Calvo Pérez, Andrés
AU - Rehkugler, Sabine
AU - Javier Agüera, Francisco
AU - Bande Seisdedos, Azucena
AU - Fernández Castaño, Jesüs
AU - Gallardo Ferrer, Roser
AU - Alomar Castell, Margalida
AU - Manzanares Mir, Concha
AU - Carrascosa Martín, Carmen
AU - Sánchez-Puga Crusat, Teresa
AU - Crespí Rullan, Joana
AU - Serra Calafat, Catalina
AU - Artigues Mascaró, Catalina
AU - Cladera Riera, Antonia
AU - Guardiola Martínez, Joana
AU - Pujol Ferragut, Margalida
AU - Aguilar González, Rocío
AU - Juan Clar, Miquel
AU - Tubau, Albert
AU - Antonia Ferragut, Maria
AU - Portells Miralles, Elena
AU - Ribera Gómez, Carmen
AU - Holster, Jessica
AU - de Oca, Elena Montes
AU - García, Dolores
AU - Vallejo Burgada, Carmen
AU - Hernández, Agustín
AU - Trias Rojas, Juan
AU - Pomar, Ines
AU - Boyeras, Joana
AU - Navarro, Eva
AU - Vives Fuster, Yolanda
AU - Maimó Vaquer, María
AU - Garces Más, Mariana
AU - Taylor, Matteu
AU - Miralles Corrales, Silvia
AU - GarcíaBaratas, Marian
AU - Blanco García, María A.
AU - Group for the study of FXS in the Balearic Islands
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - There are no reported studies to determine incidence of Fragile X Syndrome (FXS) in women within the Spanish population. For this reason, together with the high incidence of FXS in the general population, the exclusively maternal expansion, the familial and social impact of the syndrome, and the ease of use and level of detection of current PCR-based techniques, we have conducted a population-based screening pilot program of which we present here the molecular results. We typed prospectively 3,413 pregnant and 318 non-pregnant women and found a prevalence of premutation (PM) carriers of 1 in 106, which is the highest described to date in any population. We also found 230 different alleles of which the most frequent are 10A9A9 (38.4%), 9A9A9 (15.1%), and 10A9 (10.5%). Furthermore, alleles with 0 AGG interruptions or with a pure (uninterrupted) CGG repeat run larger than 34 (presumably more unstable), were more frequent among PM alleles compared to normal alleles. Theà unexpected high frequency of expanded PM alleles in females in the general population makes a very compelling argument for the need for prenatal or preconceptional FXS screening in our community. Furthermore, we find FMR1 triplet primed PCR (TP-PCR) confidently and precisely determines sizes for both alleles of the CGG repeat in women and offers AGG information which greatly improves CGG expansion risk estimations for genetic counselling. Thus, TP-PCR is an informative, efficient and robust method for FXS screening in the female population.
AB - There are no reported studies to determine incidence of Fragile X Syndrome (FXS) in women within the Spanish population. For this reason, together with the high incidence of FXS in the general population, the exclusively maternal expansion, the familial and social impact of the syndrome, and the ease of use and level of detection of current PCR-based techniques, we have conducted a population-based screening pilot program of which we present here the molecular results. We typed prospectively 3,413 pregnant and 318 non-pregnant women and found a prevalence of premutation (PM) carriers of 1 in 106, which is the highest described to date in any population. We also found 230 different alleles of which the most frequent are 10A9A9 (38.4%), 9A9A9 (15.1%), and 10A9 (10.5%). Furthermore, alleles with 0 AGG interruptions or with a pure (uninterrupted) CGG repeat run larger than 34 (presumably more unstable), were more frequent among PM alleles compared to normal alleles. Theà unexpected high frequency of expanded PM alleles in females in the general population makes a very compelling argument for the need for prenatal or preconceptional FXS screening in our community. Furthermore, we find FMR1 triplet primed PCR (TP-PCR) confidently and precisely determines sizes for both alleles of the CGG repeat in women and offers AGG information which greatly improves CGG expansion risk estimations for genetic counselling. Thus, TP-PCR is an informative, efficient and robust method for FXS screening in the female population.
KW - FMR1 gene
KW - intellectual disability
KW - neurogenetic disorder
KW - premutation
KW - prenatal screening
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U2 - 10.1002/ajmg.b.32470
DO - 10.1002/ajmg.b.32470
M3 - Article
C2 - 27333191
AN - SCOPUS:84977137252
SN - 1552-4841
VL - 171
SP - 1023
EP - 1031
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 8
ER -