TY - JOUR
T1 - Expanding the KIF4A-associated phenotype
AU - Kalantari, Silvia
AU - Carlston, Colleen
AU - Alsaleh, Norah
AU - Abdel-Salam, Ghada M.H.
AU - Alkuraya, Fowzan
AU - Kato, Mitsuhiro
AU - Matsumoto, Naomichi
AU - Miyatake, Satoko
AU - Yamamoto, Tatsuya
AU - Fares-Taie, Lucas
AU - Rozet, Jean Michel
AU - Chassaing, Nicolas
AU - Vincent-Delorme, Catherine
AU - Kang-Bellin, Anjeung
AU - McWalter, Kirsty
AU - Bupp, Caleb
AU - Palen, Emily
AU - Wagner, Monisa D.
AU - Niceta, Marcello
AU - Cesario, Claudia
AU - Milone, Roberta
AU - Kaplan, Julie
AU - Wadman, Erin
AU - Dobyns, William B.
AU - Filges, Isabel
N1 - Funding Information:
The work was supported by the Swiss National science Foundation (SNSF), Project Grant (320031_160200) and the University of Basel Research Fund to Isabel Filges.
Publisher Copyright:
© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
PY - 2021/12
Y1 - 2021/12
N2 - Kinesin super family (KIF) genes encode motor kinesins, a family of evolutionary conserved proteins, involved in intracellular trafficking of various cargoes. These proteins are critical for various physiological processes including neuron function and survival, ciliary function and ciliogenesis, and cell-cycle progression. Recent evidence suggests that alterations in motor kinesin genes can lead to a variety of human diseases, including monogenic disorders. Neuropathies, impaired higher brain functions, structural brain abnormalities and multiple congenital anomalies (i.e., renal, urogenital, and limb anomalies) can result from pathogenic variants in many KIF genes. We expand the phenotype associated with KIF4A variants from developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of phenotypic manifestations. Additional anomalies of the kidneys and urinary tract, congenital lymphedema, eye, and dental anomalies seem to be variably associated and overlap with clinical signs observed in other kinesinopathies. Caution still applies to missense variants, but hopefully, future work will further establish genotype–phenotype correlations in a larger number of patients and functional studies may give further insights into the complex function of KIF4A.
AB - Kinesin super family (KIF) genes encode motor kinesins, a family of evolutionary conserved proteins, involved in intracellular trafficking of various cargoes. These proteins are critical for various physiological processes including neuron function and survival, ciliary function and ciliogenesis, and cell-cycle progression. Recent evidence suggests that alterations in motor kinesin genes can lead to a variety of human diseases, including monogenic disorders. Neuropathies, impaired higher brain functions, structural brain abnormalities and multiple congenital anomalies (i.e., renal, urogenital, and limb anomalies) can result from pathogenic variants in many KIF genes. We expand the phenotype associated with KIF4A variants from developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of phenotypic manifestations. Additional anomalies of the kidneys and urinary tract, congenital lymphedema, eye, and dental anomalies seem to be variably associated and overlap with clinical signs observed in other kinesinopathies. Caution still applies to missense variants, but hopefully, future work will further establish genotype–phenotype correlations in a larger number of patients and functional studies may give further insights into the complex function of KIF4A.
KW - KIF4A
KW - brain anomalies
KW - hydrocephalus
KW - intellectual disability
KW - kinesinopathies
KW - kinesins
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U2 - 10.1002/ajmg.a.62443
DO - 10.1002/ajmg.a.62443
M3 - Article
C2 - 34346154
AN - SCOPUS:85111759321
SN - 1552-4825
VL - 185
SP - 3728
EP - 3739
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 12
ER -