TY - JOUR
T1 - Filamin A mutation associated with normal reading skills and dyslexia in a family with periventricular heterotopia
AU - Reinstein, Eyal
AU - Chang, Bernard S.
AU - Robertson, Stephen P.
AU - Rimoin, David L.
AU - Katzir, Tami
PY - 2012/8
Y1 - 2012/8
N2 - Periventricular heterotopia (PH) is a disorder of neuronal migration during fetal development that is characterized by morphologically normal neurons being located in an anatomically abnormal position in the mature brain. PH is usually diagnosed in patients presenting with a seizure disorder, when neuroimaging demonstrates the ectopically placed nodules of neurons. PH is a genetically and phenotypically heterogeneous disorder. The most commonly identified genetic cause is the X-linked dominant inheritance of mutations in the Filamin A (FLNA) gene. Multiple lines of evidence support the contribution of genetic factors in dyslexia. As dyslexia does not show a single-gene pattern of inheritance, it is classified as a complex genetic disorder. We have recently identified a specific reading fluency deficit in a variable group of patients with PH, in the context of normal intelligence. Here, we present a study of a mother-daughter pair who share bilateral widespread gray matter heterotopia caused by a novel mutation in FLNA and the same pattern of X-chromosome inactivation but who exhibit divergent reading and cognitive profiles. This novel observation highlights the uncertainty of using heterotopia anatomy in clinical practice to predict behavioral outcome.
AB - Periventricular heterotopia (PH) is a disorder of neuronal migration during fetal development that is characterized by morphologically normal neurons being located in an anatomically abnormal position in the mature brain. PH is usually diagnosed in patients presenting with a seizure disorder, when neuroimaging demonstrates the ectopically placed nodules of neurons. PH is a genetically and phenotypically heterogeneous disorder. The most commonly identified genetic cause is the X-linked dominant inheritance of mutations in the Filamin A (FLNA) gene. Multiple lines of evidence support the contribution of genetic factors in dyslexia. As dyslexia does not show a single-gene pattern of inheritance, it is classified as a complex genetic disorder. We have recently identified a specific reading fluency deficit in a variable group of patients with PH, in the context of normal intelligence. Here, we present a study of a mother-daughter pair who share bilateral widespread gray matter heterotopia caused by a novel mutation in FLNA and the same pattern of X-chromosome inactivation but who exhibit divergent reading and cognitive profiles. This novel observation highlights the uncertainty of using heterotopia anatomy in clinical practice to predict behavioral outcome.
KW - Dyslexia
KW - Filamin A
KW - Periventricular heterotopia
UR - http://www.scopus.com/inward/record.url?scp=84864121940&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.35455
DO - 10.1002/ajmg.a.35455
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C2 - 22740120
AN - SCOPUS:84864121940
SN - 1552-4825
VL - 158 A
SP - 1897
EP - 1901
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 8
ER -