Clinical characterization of individuals with the distal 1q21.1 microdeletion. / Edwards, Stacey D.; Schulze, Katharina V.; Rosenfeld, Jill A.; Westerfield, Lauren E.; Gerard, Amanda; Yuan, Bo; Grigorenko, Elena L. ; Posey, Jennifer E.; Bi, Weimin; Liu, Pengfei.
In: American Journal of Medical Genetics, Part A, Vol. 185, No. 5, 01.05.2021, p. 1388-1398.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Clinical characterization of individuals with the distal 1q21.1 microdeletion
AU - Edwards, Stacey D.
AU - Schulze, Katharina V.
AU - Rosenfeld, Jill A.
AU - Westerfield, Lauren E.
AU - Gerard, Amanda
AU - Yuan, Bo
AU - Grigorenko, Elena L.
AU - Posey, Jennifer E.
AU - Bi, Weimin
AU - Liu, Pengfei
N1 - Publisher Copyright: © 2021 Wiley Periodicals LLC
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Distal 1q21.1 microdeletions have shown highly variable clinical expressivity and incomplete penetrance, with affected individuals manifesting a broad spectrum of nonspecific features. The goals of this study were to better describe the phenotypic spectrum of patients with distal 1q21.1 microdeletions and to compare the clinical features among affected individuals. We performed a retrospective chart review of 47 individuals with distal 1q21.1 microdeletions tested at a large clinical genetic testing laboratory, with most patients being clinically evaluated in the same children's hospital. Health information such as growth charts, results of imaging studies, developmental history, and progress notes were collected. Statistical analysis was performed using Fisher's exact test to compare clinical features among study subjects. Common features in our cohort include microcephaly (51.2%), seizures (29.8%), developmental delay (74.5%), failure to thrive (FTT) (68.1%), dysmorphic features (63.8%), and a variety of congenital anomalies such as cardiac abnormalities (23.4%) and genitourinary abnormalities (19.1%). Compared to prior literature, we found that seizures, brain anomalies, and FTT were more prevalent among our study cohort. Females were more likely than males to have microcephaly (p = 0.0199) and cardiac abnormalities (p = 0.0018). Based on existing genome-wide clinical testing results, at least a quarter of the cohort had additional genetic findings that may impact the phenotype of the individual. Our study represents the largest cohort of distal 1q21.1 microdeletion carriers available in the literature thus far, and it further illustrates the wide spectrum of clinical manifestations among symptomatic individuals. These results may allow for improved genetic counseling and management of affected individuals. Future studies may help to elucidate the underlying molecular mechanisms impacting the phenotypic variability observed with this microdeletion.
AB - Distal 1q21.1 microdeletions have shown highly variable clinical expressivity and incomplete penetrance, with affected individuals manifesting a broad spectrum of nonspecific features. The goals of this study were to better describe the phenotypic spectrum of patients with distal 1q21.1 microdeletions and to compare the clinical features among affected individuals. We performed a retrospective chart review of 47 individuals with distal 1q21.1 microdeletions tested at a large clinical genetic testing laboratory, with most patients being clinically evaluated in the same children's hospital. Health information such as growth charts, results of imaging studies, developmental history, and progress notes were collected. Statistical analysis was performed using Fisher's exact test to compare clinical features among study subjects. Common features in our cohort include microcephaly (51.2%), seizures (29.8%), developmental delay (74.5%), failure to thrive (FTT) (68.1%), dysmorphic features (63.8%), and a variety of congenital anomalies such as cardiac abnormalities (23.4%) and genitourinary abnormalities (19.1%). Compared to prior literature, we found that seizures, brain anomalies, and FTT were more prevalent among our study cohort. Females were more likely than males to have microcephaly (p = 0.0199) and cardiac abnormalities (p = 0.0018). Based on existing genome-wide clinical testing results, at least a quarter of the cohort had additional genetic findings that may impact the phenotype of the individual. Our study represents the largest cohort of distal 1q21.1 microdeletion carriers available in the literature thus far, and it further illustrates the wide spectrum of clinical manifestations among symptomatic individuals. These results may allow for improved genetic counseling and management of affected individuals. Future studies may help to elucidate the underlying molecular mechanisms impacting the phenotypic variability observed with this microdeletion.
KW - 1q21.1 deletion
KW - chromosomal microarray
KW - copy number variant
KW - developmental delay
KW - neuropsychiatric disorder
KW - 1q21.1 deletion
KW - chromosomal microarray
KW - copy number variant
KW - developmental delay
KW - neuropsychiatric disorder
KW - Humans
KW - Child, Preschool
KW - Infant
KW - Male
KW - Genetic Counseling
KW - Young Adult
KW - Chromosomes, Human, Pair 1/genetics
KW - Failure to Thrive/complications
KW - Intellectual Disability/complications
KW - Microcephaly/complications
KW - Adult
KW - Female
KW - Child
KW - Chromosome Deletion
KW - Megalencephaly/complications
KW - Seizures/complications
KW - Developmental Disabilities/complications
KW - Heart Defects, Congenital/complications
KW - Genetic Testing/methods
KW - Pedigree
KW - Adolescent
KW - DNA Copy Number Variations/genetics
KW - Abnormalities, Multiple/diagnosis
KW - 1q21
KW - 1 deletion
UR - https://www.mendeley.com/catalogue/56257951-2e61-3ab7-abc5-f479bec460a6/
UR - http://www.scopus.com/inward/record.url?scp=85101034920&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.62104
DO - 10.1002/ajmg.a.62104
M3 - Article
C2 - 33576134
VL - 185
SP - 1388
EP - 1398
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 5
ER -
ID: 87397735