TY - JOUR
T1 - Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications
AU - Szafranski, Przemyslaw
AU - Golla, Sailaja
AU - Jin, Weihong
AU - Fang, Ping
AU - Hixson, Patricia
AU - Matalon, Reuben
AU - Kinney, Daniel
AU - Bock, Hans Georg
AU - Craigen, William
AU - Smith, Janice L.
AU - Bi, Weimin
AU - Patel, Ankita
AU - Wai Cheung, Sau
AU - Bacino, Carlos A.
AU - Stankiewicz, Paweł
N1 - Publisher Copyright:
© 2015 Macmillan Publishers Limited All rights reserved.
PY - 2015/7/12
Y1 - 2015/7/12
N2 - Point mutations and genomic deletions of the CDKL5 (STK9) gene on chromosome Xp22 have been reported in patients with severe neurodevelopmental abnormalities, including Rett-like disorders. To date, only larger-sized (8-21 Mb) duplications harboring CDKL5 have been described. We report seven females and four males from seven unrelated families with CDKL5 duplications 540-935 kb in size. Three families of different ethnicities had identical 667kb duplications containing only the shorter CDKL5 isoform. Four affected boys, 8-14 years of age, and three affected girls, 6-8 years of age, manifested autistic behavior, developmental delay, language impairment, and hyperactivity. Of note, two boys and one girl had macrocephaly. Two carrier mothers of the affected boys reported a history of problems with learning and mathematics while at school. None of the patients had epilepsy. Similarly to CDKL5 mutations and deletions, the X-inactivation pattern in all six studied females was random. We hypothesize that the increased dosage of CDKL5 might have affected interactions of this kinase with its substrates, leading to perturbation of synaptic plasticity and learning, and resulting in autistic behavior, developmental and speech delay, hyperactivity, and macrocephaly.
AB - Point mutations and genomic deletions of the CDKL5 (STK9) gene on chromosome Xp22 have been reported in patients with severe neurodevelopmental abnormalities, including Rett-like disorders. To date, only larger-sized (8-21 Mb) duplications harboring CDKL5 have been described. We report seven females and four males from seven unrelated families with CDKL5 duplications 540-935 kb in size. Three families of different ethnicities had identical 667kb duplications containing only the shorter CDKL5 isoform. Four affected boys, 8-14 years of age, and three affected girls, 6-8 years of age, manifested autistic behavior, developmental delay, language impairment, and hyperactivity. Of note, two boys and one girl had macrocephaly. Two carrier mothers of the affected boys reported a history of problems with learning and mathematics while at school. None of the patients had epilepsy. Similarly to CDKL5 mutations and deletions, the X-inactivation pattern in all six studied females was random. We hypothesize that the increased dosage of CDKL5 might have affected interactions of this kinase with its substrates, leading to perturbation of synaptic plasticity and learning, and resulting in autistic behavior, developmental and speech delay, hyperactivity, and macrocephaly.
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U2 - 10.1038/ejhg.2014.217
DO - 10.1038/ejhg.2014.217
M3 - Article
C2 - 25315662
AN - SCOPUS:84930870955
SN - 1018-4813
VL - 23
SP - 915
EP - 921
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 7
ER -