Prenatal diagnosis of a 0.7-Mb 17p13.3 microdeletion encompassing YWHAE and CRK but not PAFAH1B1 in a fetus without ultrasound abnormalities

Chen, Chih‐Ping; Ko, Tsang‐Ming; Wang, Liang-Kai; Chern, Schu‐Rern; Wu, Peih-Shan; Chen, Shin-Wen; Lai, Shih-Ting; Chuang, Tzu-Yun; Yang, Chien-Wen; Lee, Chen‐Chi; Wang, Wayseen

doi:10.1016/j.tjog.2017.12.022

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…It is associated with lissencephaly, epilepsy, microcephaly, growth failure, developmental delay, and dysmorphic features which include micrognathia, thin upper lip, and high forehead (Schwartz et al, 1988 ). Throughout the years, advancements have been made in the understanding of multiple genes in this microdeletion including YWHAE and PAFAH1B1 and how they impact the phenotype (Barros Fontes et al, 2017 ; Blazejewski et al, 2018 ; Bruno et al, 2010 ; Cardoso et al, 2003 ; Chen et al, 2018 ; Mignon‐Ravix et al, 2010 ; Romano et al, 2020 ; Schiff et al, 2010 ; Shimojima et al, 2010 ; Tenney et al, 2011 ). Here, we describe four individuals with 17p13.3 microdeletions that includes YWHAE with the retention of PAFAH1B1 further increasing the evidence that loss of YWHAE has detrimental effects on brain physiology.…”

Section: Discussionmentioning

confidence: 99%

Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller–Dieker syndrome

Baker

Brewer

Ferreira

et al. 2022

American J of Med Genetics Pt A

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Deletion of 17p13.3 has varying degrees of severity on brain development based on precise location and size of the deletion. The most severe phenotype is Miller-Dieker syndrome (MDS) which is characterized by lissencephaly, dysmorphic facial features, growth failure, developmental disability, and often early death. Haploinsufficiency of PAFAH1B1 is responsible for the characteristic lissencephaly in MDS. The precise role of YWHAE haploinsufficiency in MDS is unclear. Case reports are beginning to elucidate the phenotypes of individuals with 17p13.3 deletions that have deletion of YWHAE but do not include deletion of PAFAH1B1. Through our clinical genetics practice, we identified four individuals with 17p13.3 deletion that include YWHAE but not PAFAH1B1. These patients have a similar phenotype of dysmorphic facial features, developmental delay, and leukoencephalopathy. In a review of the literature, we identified 19 patients with 17p13.3 microdeletion sparing PAFAH1B1 but deleting YWHAE. Haploinsufficiency of YWHAE is associated with brain abnormalities including cystic changes. These individuals have high frequency of epilepsy, intellectual disability, and dysmorphic facial features including prominent forehead, epicanthal folds, and broad nasal root. We conclude that deletion of 17p13.3 excluding PAFAH1B1 but including YWHAE is associated with a consistent phenotype and should be considered a distinct condition from MDS.

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Section: Discussionmentioning

confidence: 99%

Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller–Dieker syndrome

Baker

Brewer

Ferreira

et al. 2022

American J of Med Genetics Pt A

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“…At present, ultrasound is thought to be another possible tool in the prenatal detection of characteristic findings associated with MDS. The sonographic abnormalities associated with MDS include CNS anomalies such as lissencephaly, corpus callosum dysgenesis/agenesis, ventriculomegaly and microcephaly, polyhydramnios, IUGR, congenital heart defects, omphalocele, and renal abnormalities (Chen et al., 2010, 2018; Fong et al., 2004; Herman TE. et al, 2008; Lin et al., 2008, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Deletion of the YWHAE and CRK genes, included in this region, in addition to PAFAH1B1 , is responsible for the most severe form of classical lissencephaly seen in MDS patients (Barros Fontes et al., 2017; Blazejewski, Bennison, Smith, & Toyo‐Oka, 2018; Cardoso et al., 2003; Emrick et al., 2019). Cases with chromosome 17p13.3 deletion but not involving PAFAH1B1 have been reported to manifest phenotypic abnormalities result in neurodevelopmental delay, postnatal growth retardation, craniofacial dysmorphisms, and mild structural brain abnormalities (Chen et al., 2018; Romano et al., 2020). PAFAH1B1 is involved in a signal transduction pathway that is important for cerebral development and haploinsufficiency of PAFAH1B1 causes MDS.…”

Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of Miller–Dieker syndrome by chromosomal microarray

Shi

Huang

et al. 2020

Annals of Human Genetics

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Objective To assess the experience on prenatal diagnosis of Miller–Dieker syndrome (MDS) to further delineate the fetal presentation of this syndrome. Methods This was a retrospective study. Fetal MDS was diagnosed prenatally by chromosomal microarray (CMA). Clinical data were reviewed for these cases, including maternal characteristics, indications for prenatal diagnosis, sonographic findings, CMA results, and pregnancy outcomes. Results Four cases were diagnosis as MDS by CMA. The most common sonographic features were ventriculomegaly (3/4) and polyhydramnios (2/4). Deletion sizes ranged from 1.5 to 5.4 Mb. All microdeletions were located at the MDS critical region and showed haploinsufficiency of the YWHAE, CRK, and PAFAH1B1. All patients chose to terminate the pregnancy. Parental chromosome analysis were preformed in three cases and demonstrated that two cases were de novo and one case was caused by inherited derivative chromosomes from parental balanced translocations. Conclusion The most common prenatal ultrasound findings of MDS were ventriculomegaly and polyhydramnios. CMA can improve diagnostic precision for detecting MDS.

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“…The gene density of chromosome 17 is the second-highest in the human genome, and it contains a large number of chromosome deletion and duplication pathogenic regions (Zody et al, 2006;Goldenberg, 2018). It has several dose-sensitive genes, such as PMP22 (Gillentine et al, 2018), PAFAH1B1 (Chen et al, 2018), YWHAE (Mignon-Ravix et al, 2010), RAI1 (Loviglio et al, 2016), and NF1 (Margraf et al, 2019), which are involved in multiple genetic diseases (Shchelochkov et al, 2010). Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) result from microdeletion and microduplication, respectively, occurring at the same location in the 17p11.2 region, resulting in changes in the dose of sensitive genes and leading to two different syndromes (Heck et al, 2012;Twentyman, 2015).…”

Section: Introductionmentioning

confidence: 99%

Prenatal Diagnosis of 17p11.2 Copy Number Abnormalities Associated With Smith–Magenis and Potocki–Lupski Syndromes in Fetuses

Cai¹,

Fu²,

Xu³

et al. 2021

Front. Genet.

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Smith-Magenis syndrome and Potocki-Lupski syndrome are rare autosomal dominant diseases. Although clinical phenotypes of adults and children have been reported, fetal ultrasonic phenotypes are rarely reported. A retrospective analysis of 6,200 pregnant women who received invasive prenatal diagnosis at Fujian Provincial Maternal and Child Health Hospital between October 2016 and January 2021 was performed. Amniotic fluid or umbilical cord blood was extracted for karyotyping and single nucleotide polymorphism array analysis. Single nucleotide polymorphism array analysis revealed six fetuses with copy number variant changes in the 17p11.2 region. Among them, one had a copy number variant microdeletion in the 17p11.2 region, which was pathogenically analyzed and diagnosed as Smith-Magenis syndrome. Five fetuses had copy number variant microduplications in the 17p11.2 region, which were pathogenically analyzed and diagnosed as Potocki-Lupski syndrome. The prenatal ultrasound phenotypes of the six fetuses were varied. The parents of two fetuses with Potocki-Lupski syndrome refused verification. Smith-Magenis syndrome in one fetus and Potocki-Lupski in another were confirmed as de novo. Potocki-Lupski syndrome in two fetuses was confirmed to be from maternal inheritance. The prenatal ultrasound phenotypes of Smith-Magenis syndrome and Potocki-Lupski syndrome in fetuses vary; single nucleotide polymorphism array analysis is a powerful diagnostic tool for these diseases. The ultrasonic phenotypes of these cases may enrich the clinical database.

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Prenatal diagnosis of a 0.7-Mb 17p13.3 microdeletion encompassing YWHAE and CRK but not PAFAH1B1 in a fetus without ultrasound abnormalities

Abstract: Fetus with 17p13.3 microdeletion without involving PAFAH1B1 may present no brain abnormalities on fetal ultra sound.

Cited by 6 publications

References 23 publications

Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller–Dieker syndrome

Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller–Dieker syndrome

Prenatal diagnosis of Miller–Dieker syndrome by chromosomal microarray

Prenatal Diagnosis of 17p11.2 Copy Number Abnormalities Associated With Smith–Magenis and Potocki–Lupski Syndromes in Fetuses

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