TY - JOUR
T1 - Developmental delay and failure to thrive associated with a loss-of-function variant in WHSC1 (NSD2)
AU - Boczek, Nicole J.
AU - Lahner, Carrie A.
AU - Nguyen, Thuy mi
AU - Ferber, Matthew J.
AU - Hasadsri, Linda
AU - Thorland, Erik C.
AU - Niu, Zhiyv
AU - Gavrilova, Ralitza H.
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2018/12
Y1 - 2018/12
N2 - Wolf-Hirschhorn syndrome (WHS) is a microdeletion syndrome characterized by distinctive facial features consisting of “Greek warrior helmet” appearance, prenatal and postnatal growth deficiency, developmental disability, and seizures. This disorder is caused by heterozygous deletions on chromosome 4p16.3 often identified by cytogenetic techniques. Many groups have attempted to identify the critical region within this deletion to establish which genes are responsible for WHS. Herein, clinical whole exome sequencing (WES) was performed on a child with developmental delays, mild facial dysmorphisms, short stature, failure to thrive, and microcephaly, and revealed a de novo frameshift variant, c.1676_1679del (p.Arg559Tfs*38), in WHSC1 (NSD2). While WHSC1 falls within the WHS critical region, individuals with only disruption of this gene have only recently been described in the literature. Loss-of-function de novo variations in WHSC1 were identified in large developmental delay, autism, diagnostic, and congenital cardiac cohorts, as well as recent case reports, suggesting that de novo loss-of-function WHSC1 variants may be related to disease. These findings, along with our patient suggest that loss-of-function variation in WHSC1 may lead to a mild form of Wolf-Hirschhorn syndrome, and also may suggest that the developmental delays, facial dysmorphisms, and short stature seen in WHS may be due to disruption of WHSC1 gene.
AB - Wolf-Hirschhorn syndrome (WHS) is a microdeletion syndrome characterized by distinctive facial features consisting of “Greek warrior helmet” appearance, prenatal and postnatal growth deficiency, developmental disability, and seizures. This disorder is caused by heterozygous deletions on chromosome 4p16.3 often identified by cytogenetic techniques. Many groups have attempted to identify the critical region within this deletion to establish which genes are responsible for WHS. Herein, clinical whole exome sequencing (WES) was performed on a child with developmental delays, mild facial dysmorphisms, short stature, failure to thrive, and microcephaly, and revealed a de novo frameshift variant, c.1676_1679del (p.Arg559Tfs*38), in WHSC1 (NSD2). While WHSC1 falls within the WHS critical region, individuals with only disruption of this gene have only recently been described in the literature. Loss-of-function de novo variations in WHSC1 were identified in large developmental delay, autism, diagnostic, and congenital cardiac cohorts, as well as recent case reports, suggesting that de novo loss-of-function WHSC1 variants may be related to disease. These findings, along with our patient suggest that loss-of-function variation in WHSC1 may lead to a mild form of Wolf-Hirschhorn syndrome, and also may suggest that the developmental delays, facial dysmorphisms, and short stature seen in WHS may be due to disruption of WHSC1 gene.
KW - NSD2
KW - WHSC1
KW - developmental delay
KW - short stature
KW - whole exome sequencing
KW - wolf-Hirschhorn syndrome
UR - http://www.scopus.com/inward/record.url?scp=85055266709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055266709&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.40498
DO - 10.1002/ajmg.a.40498
M3 - Article
C2 - 30345613
AN - SCOPUS:85055266709
SN - 1552-4825
VL - 176
SP - 2798
EP - 2802
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 12
ER -