Abstract
Atypical phenotype of an imprinting disease can develop with a recessive homozygous variant due to uniparental isodisomy. We present a girl with severe intellectual disability, developmental delay, distinctive facial features, and other neuropsychiatric features. Trio whole exome sequencing revealed a novel homozygous frameshift variant in AP4E1 [NM_007347.5:c.2412dupT:p.(Gly805Trpfs*8)] and uniparental isodisomy of chromosome 15 [iUPD(15)]. Single nucleotide polymorphism mapping analysis of exome data showed that the homozygous AP4E1 variant was derived from her heterozygous carrier father and unmasked by paternal iUPD(15). Brain magnetic resonance imaging confirmed the brain abnormalities characteristic of AP4 deficiency including the dilated ventricles and hypointensity in the globus pallidus in susceptibility-weighted imaging. This is the first case report of a combination of AP4E1 deficiency and Angelman syndrome. Our patient indicates that whole exome sequencing could uncover an atypical phenotype caused by multiple genetic factors including the uniparental isodisomy.
| Original language | English |
|---|---|
| Journal | Brain and Development |
| DOIs | |
| Publication status | Accepted/In press - 2020 Jan 1 |
Fingerprint
Keywords
- Angelman syndrome
- AP4E1
- Blended phenotype
- The neurodegeneration with brain iron accumulation (NBIA)
- Uniparental isodisomy
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Developmental Neuroscience
- Clinical Neurology
Cite this
Blended phenotype of AP4E1 deficiency and Angelman syndrome caused by paternal isodisomy of chromosome 15. / Murakami, Hiroaki; Uehara, Tomoko; Tsurusaki, Yoshinori; Enomoto, Yumi; Kuroda, Yukiko; Aida, Noriko; Kosaki, Kenjiro; Kurosawa, Kenji.
In: Brain and Development, 01.01.2020.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Blended phenotype of AP4E1 deficiency and Angelman syndrome caused by paternal isodisomy of chromosome 15
AU - Murakami, Hiroaki
AU - Uehara, Tomoko
AU - Tsurusaki, Yoshinori
AU - Enomoto, Yumi
AU - Kuroda, Yukiko
AU - Aida, Noriko
AU - Kosaki, Kenjiro
AU - Kurosawa, Kenji
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Atypical phenotype of an imprinting disease can develop with a recessive homozygous variant due to uniparental isodisomy. We present a girl with severe intellectual disability, developmental delay, distinctive facial features, and other neuropsychiatric features. Trio whole exome sequencing revealed a novel homozygous frameshift variant in AP4E1 [NM_007347.5:c.2412dupT:p.(Gly805Trpfs*8)] and uniparental isodisomy of chromosome 15 [iUPD(15)]. Single nucleotide polymorphism mapping analysis of exome data showed that the homozygous AP4E1 variant was derived from her heterozygous carrier father and unmasked by paternal iUPD(15). Brain magnetic resonance imaging confirmed the brain abnormalities characteristic of AP4 deficiency including the dilated ventricles and hypointensity in the globus pallidus in susceptibility-weighted imaging. This is the first case report of a combination of AP4E1 deficiency and Angelman syndrome. Our patient indicates that whole exome sequencing could uncover an atypical phenotype caused by multiple genetic factors including the uniparental isodisomy.
AB - Atypical phenotype of an imprinting disease can develop with a recessive homozygous variant due to uniparental isodisomy. We present a girl with severe intellectual disability, developmental delay, distinctive facial features, and other neuropsychiatric features. Trio whole exome sequencing revealed a novel homozygous frameshift variant in AP4E1 [NM_007347.5:c.2412dupT:p.(Gly805Trpfs*8)] and uniparental isodisomy of chromosome 15 [iUPD(15)]. Single nucleotide polymorphism mapping analysis of exome data showed that the homozygous AP4E1 variant was derived from her heterozygous carrier father and unmasked by paternal iUPD(15). Brain magnetic resonance imaging confirmed the brain abnormalities characteristic of AP4 deficiency including the dilated ventricles and hypointensity in the globus pallidus in susceptibility-weighted imaging. This is the first case report of a combination of AP4E1 deficiency and Angelman syndrome. Our patient indicates that whole exome sequencing could uncover an atypical phenotype caused by multiple genetic factors including the uniparental isodisomy.
KW - Angelman syndrome
KW - AP4E1
KW - Blended phenotype
KW - The neurodegeneration with brain iron accumulation (NBIA)
KW - Uniparental isodisomy
UR - http://www.scopus.com/inward/record.url?scp=85077927320&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077927320&partnerID=8YFLogxK
U2 - 10.1016/j.braindev.2019.12.008
DO - 10.1016/j.braindev.2019.12.008
M3 - Article
AN - SCOPUS:85077927320
JO - Brain and Development
JF - Brain and Development
SN - 0387-7604
ER -