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Merlin G Butler - One of the best experts on this subject based on the ideXlab platform.
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the 15q11 2 bp1 bp2 microdeletion syndrome a review
International Journal of Molecular Sciences, 2015Co-Authors: Devin M Cox, Merlin G ButlerAbstract:Patients with the 15q11.2 BP1-BP2 microdeletion can present with developmental and language delay, neurobehavioral disturbances and psychiatric problems. Autism, seizures, schizophrenia and mild dysmorphic features are less commonly seen. The 15q11.2 BP1-BP2 microdeletion involving four genes (i.e., TUBGCP5, CYFIP1, NIPA1, NIPA2) is emerging as a recognized syndrome with a prevalence ranging from 0.57%-1.27% of patients presenting for microarray analysis which is a two to four fold increase compared with controls. Review of clinical features from about 200 individuals were grouped into five categories and included developmental (73%) and speech (67%) delays; dysmorphic ears (46%) and palatal anomalies (46%); writing (60%) and reading (57%) difficulties, memory problems (60%) and verbal IQ scores ≤75 (50%); general behavioral problems, unspecified (55%) and abnormal brain imaging (43%). Other clinical features noted but not considered as common were seizures/epilepsy (26%), autism spectrum disorder (27%), attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD) (35%), schizophrenia/paranoid psychosis (20%) and motor delay (42%). Not all individuals with the deletion are clinically affected, yet the collection of findings appear to share biological pathways and presumed genetic mechanisms. Neuropsychiatric and behavior disturbances and mild dysmorphic features are associated with genomic imbalances of the 15q11.2 BP1-BP2 region, including microdeletions, but with an apparent incomplete penetrance and variable expressivity.
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array comparative genomic hybridization acgh analysis in prader willi syndrome
American Journal of Medical Genetics Part A, 2008Co-Authors: Merlin G Butler, Nataliya Kibiryeva, William Fischer, Douglas C BittelAbstract:Prader–Willi syndrome (PWS) is due to loss of paternally expressed genes in the 15q11–q13 region generally from a paternal 15q11–q13 deletion. The proximal deletion breakpoint in the 15q11–q13 region occurs at one of two sites located within either of two large duplicons allowing for identification of two typical deletion subgroups. The larger type I (TI) deletion involving breakpoint 1 (BP1) is nearer to the centromere and located proximal to the microsatellite marker D15S1035, while the smaller type II (TII) deletion involves breakpoint 2 (BP2) and distal to D15S1035. Breakpoint 3 (BP3) is located at the distal end of the 15q11–q13 region and common to both typical deletion subgroups. Using high resolution aCGH, BP1 spanned a region from 18.683 to 20.220 Mb, BP2 from 20.812 to 21.357 Mb and BP3 from 25.941 to 27.286 Mb. The TI deletion ranged in size from 5.721 to 8.147 Mb (mean 6.583) and the type II deletion from 4.770 to 6.435 Mb (mean 5.330). A subset of the TI subjects showed larger deletions including the loss of at least three genes/transcripts (i.e., LOC283755, POTE5, OR4N4) in addition to the four genes between BP1 and BP2 (i.e., GCP5, CYFIP1, NIPA1, NIPA2). Interestingly, four PWS subjects had duplications of the 15q11 region in addition to the typical deletion. Furthermore, most PWS subjects had copy number variation (CNV) of 50 kb or larger in other chromosome regions; most common were deletions and duplications of 8p and 3q, previously recognized sites of CNV in the human genome. © 2008 Wiley-Liss, Inc.
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expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in prader willi syndrome
Pediatrics, 2006Co-Authors: Douglas C Bittel, Nataliya Kibiryeva, Merlin G ButlerAbstract:The authors have indicated they have no financial relationships relevant to this article to disclose. ABSTRACT Prader-Willi syndrome is a neurodevelopmental disorder that is characterized by infantile hypotonia, feeding difficulties, hypogonadism, mental deficiency, hyperphagia (leading to obesity in early childhood), learning prob- lems, and behavioral difficulties. A paternal 15q11-q13 deletion is found in 70% of patients with Prader-Willi syndrome, 25% have uniparental maternal disomy 15, and the remaining 2% to 5% have imprinting defects. The proximal deletion breakpoint in the 15q11-q13 region occurs at 1 of 2 sites located within either of 2 large duplicons allowing for the identification of 2 deletion subgroups. The larger, type I (TI) deletion involves breakpoint 1, which is close to the centromere, whereas the smaller, type II (TII) deletion involves breakpoint 2, located 500 kilobases distal to breakpoint 1. Breakpoint 3 is located at the distal end of the 15q11-q13 region and common to both typical deletion subgroups. Analyses of the genetic subtypes of Prader-Willi syndrome to date have primarily compared individuals with typical deletion and uniparental maternal disomy 15 without grouping the individuals with a deletion into TI or TII. Distinct differences have been reported between individuals with Prader-Willi syndrome resulting from deletion compared with uniparental maternal disomy 15 in physical, cognitive, and behavioral parameters. We previously presented the first assessment of clinical differences in individuals with Prader-Willi syndrome categorized as having type I or II deletions. Adaptive behavior, obsessive-compulsive behaviors, reading, math, and visual-motor integration assessments were generally poorer in individuals with Prader-Willi syndrome and the TI deletion compared with subjects with Prader-Willi syndrome with the TII deletion or uniparental maternal disomy 15. Four genes (NIPA1, NIPA2, CYFIP1, and GCP5) have been identified in the chromosomal region between breakpoints 1 and 2 and are implicated in compulsive behavior and lower intellectual ability observed in individuals with Prader-Willi syndrome with TI versus TII deletions. We quantified messenger-RNA levels of these 4 genes in actively growing lymphoblastoid cells derived from 8 subjects with Prader-Willi syndrome with the TI deletion (4 males, 4 females; mean: age 25.2 8.9 years) and 9 with the TII deletion (3 males, 6 females; mean age: 19.5 5.8 years). Messenger-RNA levels were correlated with validated psychological and behavioral scales administered by trained psychologists blinded to genotype status. Messenger RNA from NIPA1, NIPA2, CYFIP1, and GCP5 was reduced but detectable in the subjects with Prader-Willi syndrome with the TI deletion, supporting biallelic expression. For the most part, messenger-RNA values were positively correlated with assessment parameters, indicating a direct
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expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in prader willi syndrome
Pediatrics, 2006Co-Authors: Douglas C Bittel, Nataliya Kibiryeva, Merlin G ButlerAbstract:Prader-Willi syndrome is a neurodevelopmental disorder that is characterized by infantile hypotonia, feeding difficulties, hypogonadism, mental deficiency, hyperphagia (leading to obesity in early childhood), learning problems, and behavioral difficulties. A paternal 15q11-q13 deletion is found in approximately 70% of patients with Prader-Willi syndrome, approximately 25% have uniparental maternal disomy 15, and the remaining 2% to 5% have imprinting defects. The proximal deletion breakpoint in the 15q11-q13 region occurs at 1 of 2 sites located within either of 2 large duplicons allowing for the identification of 2 deletion subgroups. The larger, type I (TI) deletion involves breakpoint 1, which is close to the centromere, whereas the smaller, type II (TII) deletion involves breakpoint 2, located approximately 500 kilobases distal to breakpoint 1. Breakpoint 3 is located at the distal end of the 15q11-q13 region and common to both typical deletion subgroups. Analyses of the genetic subtypes of Prader-Willi syndrome to date have primarily compared individuals with typical deletion and uniparental maternal disomy 15 without grouping the individuals with a deletion into TI or TII. Distinct differences have been reported between individuals with Prader-Willi syndrome resulting from deletion compared with uniparental maternal disomy 15 in physical, cognitive, and behavioral parameters. We previously presented the first assessment of clinical differences in individuals with Prader-Willi syndrome categorized as having type I or II deletions. Adaptive behavior, obsessive-compulsive behaviors, reading, math, and visual-motor integration assessments were generally poorer in individuals with Prader-Willi syndrome and the TI deletion compared with subjects with Prader-Willi syndrome with the TII deletion or uniparental maternal disomy 15. Four genes (NIPA1, NIPA2, CYFIP1, and GCP5) have been identified in the chromosomal region between breakpoints 1 and 2 and are implicated in compulsive behavior and lower intellectual ability observed in individuals with Prader-Willi syndrome with TI versus TII deletions. We quantified messenger-RNA levels of these 4 genes in actively growing lymphoblastoid cells derived from 8 subjects with Prader-Willi syndrome with the TI deletion (4 males, 4 females; mean: age 25.2 +/- 8.9 years) and 9 with the TII deletion (3 males, 6 females; mean age: 19.5 +/- 5.8 years). Messenger-RNA levels were correlated with validated psychological and behavioral scales administered by trained psychologists blinded to genotype status. Messenger RNA from NIPA1, NIPA2, CYFIP1, and GCP5 was reduced but detectable in the subjects with Prader-Willi syndrome with the TI deletion, supporting biallelic expression. For the most part, messenger-RNA values were positively correlated with assessment parameters, indicating a direct relationship between messenger-RNA levels and better assessment scores, with the highest correlation for NIPA2. The coefficient of determination indicated the quantity of messenger RNA of the 4 genes explained from 24% to 99% of the variation of the behavioral and academic parameters measured. By comparison, the coefficient of determination for deletion type alone explained 5% to 50% of the variation in the assessed parameters. Understanding the influence of gene expression on behavioral and cognitive characteristics in humans is in the early stage of research development. Additional research is needed to identify the function of these genes and their interaction with gene networks to clarify the potential role they play in central nervous system development and function.
Robert D Nicholls - One of the best experts on this subject based on the ideXlab platform.
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identification of four highly conserved genes between breakpoint hotspots bp1 and bp2 of the prader willi angelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons
American Journal of Human Genetics, 2003Co-Authors: Jing Hua Chai, Devin P Locke, John M Greally, Joan H M Knoll, Tohru Ohta, Judith Dunai, Amy M Yavor, Evan E Eichler, Robert D NichollsAbstract:Prader-Willi and Angelman syndromes (PWS and AS) typically result from an ∼4-Mb deletion of human chromosome 15q11-q13, with clustered breakpoints (BP) at either of two proximal sites (BP1 and BP2) and one distal site (BP3). HERC2 and other duplicons map to these BP regions, with the 2-Mb PWS/AS imprinted domain just distal of BP2. Previously, the presence of genes and their imprinted status have not been examined between BP1 and BP2. Here, we identify two known (CYFIP1 and GCP5) and two novel (NIPA1 and NIPA2) genes in this region in human and their orthologs in mouse chromosome 7C. These genes are expressed from a broad range of tissues and are nonimprinted, as they are expressed in cells derived from normal individuals, patients with PWS or AS, and the corresponding mouse models. However, replication-timing studies in the mouse reveal that they are located in a genomic domain showing asynchronous replication, a feature typically ascribed to monoallelically expressed loci. The novel genes NIPA1 and NIPA2 each encode putative polypeptides with nine transmembrane domains, suggesting function as receptors or as transporters. Phylogenetic analyses show that NIPA1 and NIPA2 are highly conserved in vertebrate species, with ancestral members in invertebrates and plants. Intriguingly, evolutionary studies show conservation of the four-gene cassette between BP1 and BP2 in human, including NIPA1/2, CYFIP1, and GCP5, and proximity to the Herc2 gene in both mouse and Fugu. These observations support a model in which duplications of the HERC2 gene at BP3 in primates first flanked the four-gene cassette, with subsequent transposition of these four unique genes by a HERC2 duplicon-mediated process to form the BP1–BP2 region. Duplicons therefore appear to mediate genomic fluidity in both disease and evolutionary processes.
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NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia spg6
American Journal of Human Genetics, 2003Co-Authors: Shirley Rainier, Jing Hua Chai, Robert D Nicholls, Debra A Tokarz, John K FinkAbstract:The hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders characterized by progressive lower-extremity weakness and spasticity. The molecular pathogenesis is poorly understood. We report discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant HSP (ADHSP), linked to chromosome 15q11-q13 (SPG6 locus); and precisely the same mutation in an unrelated kindred with ADHSP that was too small for meaningful linkage analysis. NIPA1 is highly expressed in neuronal tissues and encodes a putative membrane transporter or receptor. Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications.
Douglas C Bittel - One of the best experts on this subject based on the ideXlab platform.
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array comparative genomic hybridization acgh analysis in prader willi syndrome
American Journal of Medical Genetics Part A, 2008Co-Authors: Merlin G Butler, Nataliya Kibiryeva, William Fischer, Douglas C BittelAbstract:Prader–Willi syndrome (PWS) is due to loss of paternally expressed genes in the 15q11–q13 region generally from a paternal 15q11–q13 deletion. The proximal deletion breakpoint in the 15q11–q13 region occurs at one of two sites located within either of two large duplicons allowing for identification of two typical deletion subgroups. The larger type I (TI) deletion involving breakpoint 1 (BP1) is nearer to the centromere and located proximal to the microsatellite marker D15S1035, while the smaller type II (TII) deletion involves breakpoint 2 (BP2) and distal to D15S1035. Breakpoint 3 (BP3) is located at the distal end of the 15q11–q13 region and common to both typical deletion subgroups. Using high resolution aCGH, BP1 spanned a region from 18.683 to 20.220 Mb, BP2 from 20.812 to 21.357 Mb and BP3 from 25.941 to 27.286 Mb. The TI deletion ranged in size from 5.721 to 8.147 Mb (mean 6.583) and the type II deletion from 4.770 to 6.435 Mb (mean 5.330). A subset of the TI subjects showed larger deletions including the loss of at least three genes/transcripts (i.e., LOC283755, POTE5, OR4N4) in addition to the four genes between BP1 and BP2 (i.e., GCP5, CYFIP1, NIPA1, NIPA2). Interestingly, four PWS subjects had duplications of the 15q11 region in addition to the typical deletion. Furthermore, most PWS subjects had copy number variation (CNV) of 50 kb or larger in other chromosome regions; most common were deletions and duplications of 8p and 3q, previously recognized sites of CNV in the human genome. © 2008 Wiley-Liss, Inc.
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expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in prader willi syndrome
Pediatrics, 2006Co-Authors: Douglas C Bittel, Nataliya Kibiryeva, Merlin G ButlerAbstract:The authors have indicated they have no financial relationships relevant to this article to disclose. ABSTRACT Prader-Willi syndrome is a neurodevelopmental disorder that is characterized by infantile hypotonia, feeding difficulties, hypogonadism, mental deficiency, hyperphagia (leading to obesity in early childhood), learning prob- lems, and behavioral difficulties. A paternal 15q11-q13 deletion is found in 70% of patients with Prader-Willi syndrome, 25% have uniparental maternal disomy 15, and the remaining 2% to 5% have imprinting defects. The proximal deletion breakpoint in the 15q11-q13 region occurs at 1 of 2 sites located within either of 2 large duplicons allowing for the identification of 2 deletion subgroups. The larger, type I (TI) deletion involves breakpoint 1, which is close to the centromere, whereas the smaller, type II (TII) deletion involves breakpoint 2, located 500 kilobases distal to breakpoint 1. Breakpoint 3 is located at the distal end of the 15q11-q13 region and common to both typical deletion subgroups. Analyses of the genetic subtypes of Prader-Willi syndrome to date have primarily compared individuals with typical deletion and uniparental maternal disomy 15 without grouping the individuals with a deletion into TI or TII. Distinct differences have been reported between individuals with Prader-Willi syndrome resulting from deletion compared with uniparental maternal disomy 15 in physical, cognitive, and behavioral parameters. We previously presented the first assessment of clinical differences in individuals with Prader-Willi syndrome categorized as having type I or II deletions. Adaptive behavior, obsessive-compulsive behaviors, reading, math, and visual-motor integration assessments were generally poorer in individuals with Prader-Willi syndrome and the TI deletion compared with subjects with Prader-Willi syndrome with the TII deletion or uniparental maternal disomy 15. Four genes (NIPA1, NIPA2, CYFIP1, and GCP5) have been identified in the chromosomal region between breakpoints 1 and 2 and are implicated in compulsive behavior and lower intellectual ability observed in individuals with Prader-Willi syndrome with TI versus TII deletions. We quantified messenger-RNA levels of these 4 genes in actively growing lymphoblastoid cells derived from 8 subjects with Prader-Willi syndrome with the TI deletion (4 males, 4 females; mean: age 25.2 8.9 years) and 9 with the TII deletion (3 males, 6 females; mean age: 19.5 5.8 years). Messenger-RNA levels were correlated with validated psychological and behavioral scales administered by trained psychologists blinded to genotype status. Messenger RNA from NIPA1, NIPA2, CYFIP1, and GCP5 was reduced but detectable in the subjects with Prader-Willi syndrome with the TI deletion, supporting biallelic expression. For the most part, messenger-RNA values were positively correlated with assessment parameters, indicating a direct
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expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in prader willi syndrome
Pediatrics, 2006Co-Authors: Douglas C Bittel, Nataliya Kibiryeva, Merlin G ButlerAbstract:Prader-Willi syndrome is a neurodevelopmental disorder that is characterized by infantile hypotonia, feeding difficulties, hypogonadism, mental deficiency, hyperphagia (leading to obesity in early childhood), learning problems, and behavioral difficulties. A paternal 15q11-q13 deletion is found in approximately 70% of patients with Prader-Willi syndrome, approximately 25% have uniparental maternal disomy 15, and the remaining 2% to 5% have imprinting defects. The proximal deletion breakpoint in the 15q11-q13 region occurs at 1 of 2 sites located within either of 2 large duplicons allowing for the identification of 2 deletion subgroups. The larger, type I (TI) deletion involves breakpoint 1, which is close to the centromere, whereas the smaller, type II (TII) deletion involves breakpoint 2, located approximately 500 kilobases distal to breakpoint 1. Breakpoint 3 is located at the distal end of the 15q11-q13 region and common to both typical deletion subgroups. Analyses of the genetic subtypes of Prader-Willi syndrome to date have primarily compared individuals with typical deletion and uniparental maternal disomy 15 without grouping the individuals with a deletion into TI or TII. Distinct differences have been reported between individuals with Prader-Willi syndrome resulting from deletion compared with uniparental maternal disomy 15 in physical, cognitive, and behavioral parameters. We previously presented the first assessment of clinical differences in individuals with Prader-Willi syndrome categorized as having type I or II deletions. Adaptive behavior, obsessive-compulsive behaviors, reading, math, and visual-motor integration assessments were generally poorer in individuals with Prader-Willi syndrome and the TI deletion compared with subjects with Prader-Willi syndrome with the TII deletion or uniparental maternal disomy 15. Four genes (NIPA1, NIPA2, CYFIP1, and GCP5) have been identified in the chromosomal region between breakpoints 1 and 2 and are implicated in compulsive behavior and lower intellectual ability observed in individuals with Prader-Willi syndrome with TI versus TII deletions. We quantified messenger-RNA levels of these 4 genes in actively growing lymphoblastoid cells derived from 8 subjects with Prader-Willi syndrome with the TI deletion (4 males, 4 females; mean: age 25.2 +/- 8.9 years) and 9 with the TII deletion (3 males, 6 females; mean age: 19.5 +/- 5.8 years). Messenger-RNA levels were correlated with validated psychological and behavioral scales administered by trained psychologists blinded to genotype status. Messenger RNA from NIPA1, NIPA2, CYFIP1, and GCP5 was reduced but detectable in the subjects with Prader-Willi syndrome with the TI deletion, supporting biallelic expression. For the most part, messenger-RNA values were positively correlated with assessment parameters, indicating a direct relationship between messenger-RNA levels and better assessment scores, with the highest correlation for NIPA2. The coefficient of determination indicated the quantity of messenger RNA of the 4 genes explained from 24% to 99% of the variation of the behavioral and academic parameters measured. By comparison, the coefficient of determination for deletion type alone explained 5% to 50% of the variation in the assessed parameters. Understanding the influence of gene expression on behavioral and cognitive characteristics in humans is in the early stage of research development. Additional research is needed to identify the function of these genes and their interaction with gene networks to clarify the potential role they play in central nervous system development and function.
Jing Hua Chai - One of the best experts on this subject based on the ideXlab platform.
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identification of four highly conserved genes between breakpoint hotspots bp1 and bp2 of the prader willi angelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons
American Journal of Human Genetics, 2003Co-Authors: Jing Hua Chai, Devin P Locke, John M Greally, Joan H M Knoll, Tohru Ohta, Judith Dunai, Amy M Yavor, Evan E Eichler, Robert D NichollsAbstract:Prader-Willi and Angelman syndromes (PWS and AS) typically result from an ∼4-Mb deletion of human chromosome 15q11-q13, with clustered breakpoints (BP) at either of two proximal sites (BP1 and BP2) and one distal site (BP3). HERC2 and other duplicons map to these BP regions, with the 2-Mb PWS/AS imprinted domain just distal of BP2. Previously, the presence of genes and their imprinted status have not been examined between BP1 and BP2. Here, we identify two known (CYFIP1 and GCP5) and two novel (NIPA1 and NIPA2) genes in this region in human and their orthologs in mouse chromosome 7C. These genes are expressed from a broad range of tissues and are nonimprinted, as they are expressed in cells derived from normal individuals, patients with PWS or AS, and the corresponding mouse models. However, replication-timing studies in the mouse reveal that they are located in a genomic domain showing asynchronous replication, a feature typically ascribed to monoallelically expressed loci. The novel genes NIPA1 and NIPA2 each encode putative polypeptides with nine transmembrane domains, suggesting function as receptors or as transporters. Phylogenetic analyses show that NIPA1 and NIPA2 are highly conserved in vertebrate species, with ancestral members in invertebrates and plants. Intriguingly, evolutionary studies show conservation of the four-gene cassette between BP1 and BP2 in human, including NIPA1/2, CYFIP1, and GCP5, and proximity to the Herc2 gene in both mouse and Fugu. These observations support a model in which duplications of the HERC2 gene at BP3 in primates first flanked the four-gene cassette, with subsequent transposition of these four unique genes by a HERC2 duplicon-mediated process to form the BP1–BP2 region. Duplicons therefore appear to mediate genomic fluidity in both disease and evolutionary processes.
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NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia spg6
American Journal of Human Genetics, 2003Co-Authors: Shirley Rainier, Jing Hua Chai, Robert D Nicholls, Debra A Tokarz, John K FinkAbstract:The hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders characterized by progressive lower-extremity weakness and spasticity. The molecular pathogenesis is poorly understood. We report discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant HSP (ADHSP), linked to chromosome 15q11-q13 (SPG6 locus); and precisely the same mutation in an unrelated kindred with ADHSP that was too small for meaningful linkage analysis. NIPA1 is highly expressed in neuronal tissues and encodes a putative membrane transporter or receptor. Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications.
Chih-ping Chen - One of the best experts on this subject based on the ideXlab platform.
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prenatal diagnosis of a familial 15q11 2 bp1 bp2 microdeletion encompassing tubgcp5 cyfip1 nipa2 and NIPA1 in a fetus with ventriculomegaly microcephaly and intrauterine growth restriction on prenatal ultrasound
Taiwanese Journal of Obstetrics & Gynecology, 2018Co-Authors: Chih-ping Chen, Schu-rern Chern, Shin-wen Chen, Shuyuan Chang, Liangkai Wang, Tungyao Chang, Shihting Lai, Tzuyun Chuang, Chienwen Yang, Daidyi TownAbstract:Abstract Objective We present prenatal diagnosis of a 15q11.2 (BP1-BP2) microdeletion encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in a fetus with ventriculomegaly, microcephaly and intrauterine growth restriction (IUGR) on prenatal ultrasound. Case report A 30-year-old, gravida 3, para 2, woman was referred to the hospital for amniocentesis because of fetal ventriculomegaly on prenatal ultrasound. Her husband was 31 years old. The couple had two healthy daughters, and there was no family history of mental disorders and congenital malformations. Amniocentesis revealed a karyotype of 46,XX. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed a 451.89-kb 15q11.2 microdeletion or arr 15q11.2 (22,765,628–23,217,514) × 1.0 [GRCh37 (hg19)] encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1. The parental karyotypes were normal. aCGH analysis on the DNAs extracted from parental bloods revealed a 402-kb 15q11.2 microdeletion or arr 15q11.2 (22,815,577-23,217,514) × 1.0 (hg19) encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in the phenotypically normal father. The mother did not have any genomic imbalance. Level II ultrasound at 21 weeks of gestation revealed microcephaly and IUGR. The parents elected to terminate the pregnancy at 22 weeks of gestation, and a female fetus was delivered with a body weight of 448 g (10th centile) and a body length of 26 cm (3rd–10th centile) but no gross abnormalities. Conclusion Fetuses with a 15q11.2 (BP1-BP2) microdeletion may present ventriculomegaly, microcephaly and IUGR on prenatal ultrasound, and aCGH is helpful for prenatal diagnosis under such a circumstance.
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Prenatal diagnosis of a familial 15q11.2 (BP1-BP2) microdeletion encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in a fetus with ventriculomegaly, microcephaly and intrauterine growth restriction on prenatal ultrasound
'Elsevier BV', 2018Co-Authors: Chih-ping Chen, Schu-rern Chern, Shin-wen Chen, Shuyuan Chang, Liangkai Wang, Tungyao Chang, Shihting Lai, Tzuyun Chuang, Chienwen YangAbstract:Objective: We present prenatal diagnosis of a 15q11.2 (BP1-BP2) microdeletion encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in a fetus with ventriculomegaly, microcephaly and intrauterine growth restriction (IUGR) on prenatal ultrasound. Case report: A 30-year-old, gravida 3, para 2, woman was referred to the hospital for amniocentesis because of fetal ventriculomegaly on prenatal ultrasound. Her husband was 31 years old. The couple had two healthy daughters, and there was no family history of mental disorders and congenital malformations. Amniocentesis revealed a karyotype of 46,XX. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed a 451.89-kb 15q11.2 microdeletion or arr 15q11.2 (22,765,628–23,217,514) × 1.0 [GRCh37 (hg19)] encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1. The parental karyotypes were normal. aCGH analysis on the DNAs extracted from parental bloods revealed a 402-kb 15q11.2 microdeletion or arr 15q11.2 (22,815,577-23,217,514) × 1.0 (hg19) encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in the phenotypically normal father. The mother did not have any genomic imbalance. Level II ultrasound at 21 weeks of gestation revealed microcephaly and IUGR. The parents elected to terminate the pregnancy at 22 weeks of gestation, and a female fetus was delivered with a body weight of 448 g (10th centile) and a body length of 26 cm (3rd–10th centile) but no gross abnormalities. Conclusion: Fetuses with a 15q11.2 (BP1-BP2) microdeletion may present ventriculomegaly, microcephaly and IUGR on prenatal ultrasound, and aCGH is helpful for prenatal diagnosis under such a circumstance. Keywords: 15q11.2 (BP1-BP2) deletion, Microcephaly, Prenatal diagnosis, Ventriculomegal
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Familial transmission of recurrent 15q11.2 (BP1-BP2) microdeletion encompassing NIPA1, NIPA2, CYFIP1, and TUBGCP5 associated with phenotypic variability in developmental, speech, and motor delay.
Taiwanese journal of obstetrics & gynecology, 2017Co-Authors: Chih-ping Chen, Shuan-pei Lin, C. C. Lee, Schu-rern Chern, Yen-ni Chen, Shin-wen Chen, Wayseen WangAbstract:Abstract Objective We present recurrent 15q11.2 (BP1-BP2) microdeletion encompassing NIPA1 , NIPA2 , CYFIP1 , and TUBGCP5 in a family with phenotypic variability in developmental, speech, and motor delay. Case Report A 32-year-old woman underwent amniocentesis at 17 weeks of gestation because of an abnormal maternal serum screening result of Down syndrome risk of 1/226. Her husband was 31 years old. She and her husband were phenotypically normal, and there was no family history of mental disorders and congenital malformations. Amniocentesis revealed a karyotype of 46,XX. Prenatal ultrasound findings were unremarkable. A 2492-g female baby was delivered at 37 weeks of gestation uneventfully. During the subsequent pregnancy, the same woman at the age of 35 years underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, which revealed a karyotype of 46,XY. Prenatal ultrasound findings were unremarkable. A 2780-g male baby was delivered at 37 weeks of gestation uneventfully. About 3 years after the birth of this boy, array comparative genomic hybridization of the family revealed 15q11.2 microdeletion encompassing NIPA1 , NIPA2 , CYFIP1 , and TUBGCP5 in the two siblings, who displayed developmental, speech, and motor delay, and in their phenotypically normal father. Conclusion Recurrent phenotypic abnormality in the family with normal karyotype at amniocentesis should include a differential diagnosis of familial pathogenic copy-number variations.