Chromosome 1p36 Deletion Syndrome Research Articles

Prenatal diagnosis of a fetus with 1p36 deletion syndrome and 3p26.3p25.2 duplication

To explore the characteristics of a fetus with chromosome 1p36 deletion syndrome and 3p26.3p25.2 duplication. A pregnant woman who had attended the Genetic Counseling Clinic of Linyi People's Hospital on February 22, 2022 and her fetus were selected as the study subjects. Clinical data were collected. Chromosomal karyotyping, fluorescence in situ hybridization (FISH) and chromosomal microarray analysis (CMA) were carried out for the prenatal diagnosis. Ultrasonography at 24th gestational week revealed that the fetus had ventricular septal defect, single umbilical artery, and slight widening of left lateral ventricle (12 mm). The woman was found to have a karyotype of 46,XX,t(1;3)(p36.22;p25.2), and the result of FISH was t(1;3)(3pter+,1qter+;1pter+,3qter+). The fetus was found to have a karyotype of 46,X?,add(1)(p36), and CMA confirmed that it has a 9.0 Mb deletion at 1p36.33p36.22 and a 12.6 Mb duplication at 3p26.3p25.2. Combining the maternal karyotype, the molecular karyotype of the fetus was determined as 46,X?,der(1)t(1;3)(p36.22;p25.2)mat.arr[hg19]1p36.33p36.22(849467_9882666)×1, 3p26.3p25.2(61892_12699607)×3, with the former known to be associated with 1p36 deletion syndrome. The fetus was diagnosed with 1p36 deletion syndrome, and its 1p36.33p36.22 deletion and 3p26.3p25.2 duplication had both derived from the balanced translocation carried by its mother.

1p36 deletion syndrome: Review and mapping with further characterization of the phenotype, a new cohort of 86 patients.

Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype-phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.

Cardiovascular Phenotypic Spectrum of 1p36 Deletion Syndrome.

Chromosome 1p36 deletion syndrome is a common genetic anomaly (prevalence: 1 in 5,000-1 in 10,000). Despite reports of cardiovascular involvement, the cardiovascular phenotypic spectrum of patients with 1p36 deletion syndrome is not well characterized. In this article, we reported the clinical course of a full-term African American boy with chromosome 1p36 deletion syndrome and neonatal onset of severe cardiac disease with moderate-to-severe biventricular dysfunction and severe pulmonary hypertension. Early neonatal onset presentation of 1p36 deletion syndrome is rare and might be associated with a more guarded prognosis. This case based study is supplemented by a comprehensive review of cardiovascular involvement in this relatively common genetic syndrome.

Chromosome 1p36 Deletion Syndrome: Four Patients with Variable Presentations.

Chromosome 1p36 deletion accounts for around 1% of cases of intellectual disability. The pattern of clinical features includes developmental delay, hypotonia, seizures, short stature, intellectual disability, vision and hearing deficits, congenital heart disease, and renal abnormalities. The size of deletion can be variable. We report four cases of 1p36 deletion syndrome detected in the past 3 years in a genetic clinic. One patient was detected by next-generation sequencing, another by chromosomal microarray, and the remaining two by multiplex ligation-dependent probe amplification. We discuss the variable presentations in the four children. Early diagnosis enables better prognostication and further reproductive planning.

A Novel Case of Biliary Atresia in a Premature Neonate With 1p36 Deletion Syndrome.

We describe the case of a premature male neonate diagnosed with biliary atresia who was found to have chromosome 1p36 deletion syndrome. Our patient was born prematurely, at a gestational age of 28 weeks. Pregnancy was complicated by advanced maternal age, gestational hypertension, and intrauterine growth restriction. Physical examination revealed several dysmorphic features, prompting a genetic evaluation, which revealed chromosome 1p36 deletion syndrome. At week 7 of life, he was found to have acholic stools. Direct bilirubin was found to be elevated despite discontinuation of total parenteral nutrition at 3 weeks of life, thus raising the suspicion for biliary atresia. Biliary atresia was confirmed by constellation of clinical, imaging and intraoperative findings. First reported in 1996, 1p36 deletion syndrome has been researched increasingly and several new phenotypic associations have been reported over the years. While attempts at linking specific phenotypic abnormalities with individual gene(s) deletion(s) are being made, deletion patterns that would affect specific organ system or function remain to be fully understood. Thus, clinicians currently rely on reports of previously identified abnormalities. To our knowledge, our patient is the first report of biliary atresia in a patient with chromosome 1p36 deletion syndrome. It is important to determine the etiology of the cholestasis, when present, while caring for premature neonates with 1p36 deletion syndrome. This is necessary to avoid assuming that the cholestasis is arising from total parenteral nutrition administration and not from other gastrointestinal anomalies including biliary atresia, which is a time-sensitive diagnosis.

Prenatal diagnosis of two fetuses with chromosome 1p36 deletion syndrome

To analyze two fetuses with multiple malformations revealed by ultrasonography using single nucleotide polymorphism array (SNP array), and to explore the strategy for the prenatal diagnosis of 1p36 deletion syndrome. Amniocentesis was performed on the two pregnant women. Amnion fluid cells were cultured, and karyotypes of the fetuses were determined through G-banding analysis. Whole genome SNP array was used to detect genomic anomalies of the two fetuses. The karyotypes of their parents were determined through G-banding analysis of peripheral venous blood samples. G-banding analysis showed a 46,XY,add(1p36)? and a 46,XX,add(1p36)? karyotype for fetuses 1 and 2, respectively. SNP array analysis showed that the fetus 1 had arr[19]1p36.33p36.32 (752 566 - 3 393 462)×1 and 7q35q36.3 (144 480 549 - 159 119 486)×3, and fetus 2 had arr[19]1p36.33p36.23 (752 566 - 8 362 754)×1, 6p25.3p22.3 (204 909 - 20 182 185)×3. The mother of fetus 1 had a 46,XX,t(1;7)(p36;q35) karyotype, and the mother of fetus 2 had a 46,XX,t(1;6)(p36;p22) karyotype. The karyotypes of both fathers appeared to be normal. SNP array has the advantages such as high sensitivity and high accuracy for prenatal diagnosis, and can provide more detailed information for genetic counseling of 1p36 deletion syndrome.

The inner cell mass confirms deletion syndromes detected in trophectoderm biopsies

Deletion syndromes are defined as clinically recognizable genetic disorders characterized by a small chromosomal deletion, with a frequency of 0.5% in prenatal testing and 1 in 700 newborns. The cumulative effect of the imbalance on multiple independent disease genes within the deletion region determines the overall phenotype including, among others, developmental delay, intellectual disability and dysmorphic features. Many deletion syndromes have a corresponding duplication syndrome that is generally more rare and associated with a milder phenotype. Deletions and duplications are typically random events that occur during gametogenesis. The aim of this study was to evaluate the clinical reliability of diagnosing chromosomal deletions in blastocyst trophectoderm (TE) biopsies. Prospective blinded single-center study. A total of 26 blastocysts identified with small chromosome deletions, using the VeriSeq™ NGS platform (Illumina), were donated with patient consent (mean maternal age = 36.3 ±4.0years; mean paternal age = 38.6 ±6.1years). Each blastocyst was re-biopsied into three separate segments that were individually, blindly re-analyzed using the same VeriSeq™ NGS platform performed at the same genetic laboratory (n=96 samples). After un-blinding, all four segments were compiled together for a complete picture of every individual human blastocyst, including representatives of the inner cell mass (ICM) and TE. The overall incidence of partial aneuploidy following TE biopsy of 10,783 human blastocysts was observed at 1% (n=110). The blinded re-analysis of 26 blastocysts with small chromosome deletions, validated the reliability of the original deletion diagnosis in 24 (92.3%) of the embryos. The small chromosome deletion was observed throughout the entire embryo, including all ICM and TE segments, for 14 blastocysts (53.9%). The remaining blastocysts displayed evidence of potential mitotic cell division errors with either a diploid cell line in 1 TE segment (n=6; 23%), or the reverse small chromosome duplication in the re-biopsy ICM and TE segments (n=4; 15.4%). Examples of the clinically recognizable genetic disorders diagnosed in these 26 human blastocysts include chromosome 1q41-q42 deletion syndrome, chromosome 1p36 deletion syndrome, Cri-du-chat syndrome (end of chromosome 5p deletion) and chromosome 8q21.3-q22.1 deletion syndrome. This novel study validated the reliability of diagnosing chromosomal deletion syndromes in blastocyst biopsies. Our re-analysis results confirmed the original partial aneuploidy diagnosis to be present throughout the corresponding blastocyst with no preferential allocation to trophectoderm cells. These observed embryonic chromosomal deletions have been clearly associated with clinically recognizable genetic disorders.

Detection of 1p36 deletion by clinical exome-first diagnostic approach.

Although chromosome 1p36 deletion syndrome is considered clinically recognizable based on characteristic features, the clinical manifestations of patients during infancy are often not consistent with those observed later in life. We report a 4-month-old girl who showed multiple congenital anomalies and developmental delay, but no clinical signs of syndromic disease caused by a terminal deletion in 1p36.32-p36.33 that was first identified by targeted-exome sequencing for molecular diagnosis.

Follicular Bronchiolitis in a Child With 1p36 Deletion Syndrome

SESSION TITLE: Lung Pathology Student/Resident Case Report Posters SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 27, 2015 at 01:30 PM - 02:30 PM INTRODUCTION: The rarity of pulmonary manifestations in children with chromosome 1p36 deletion syndrome makes a diagnosis of follicular bronchiolitis (FB) a unique challenge. CASE PRESENTATION: A one year old female was diagnosed with a chromosome 1p36 deletion after birth. She has hypotonia, developmental delay, visual abnormalities, growth and feeding related problems, which are common features of this disorder. She presented with tachypnea, several months of productive cough and wheezing that were unresponsive to antibiotics, albuterol, and corticosteroids. On exam, she was dysmorphic, hypotonic, with increased respiratory distress, and mild splenomegaly. A chest CT showed compression of the right upper lobe (RUL) bronchus and an ill-defined soft tissue fullness in right hilum. She was admitted with concern for neuroblastoma and immunodeficiency. An extensive autoimmune, infectious, and immunodeficiency work-up was negative, except for a low CD4/CD8 ratio. She was found to have elevated metanephrines; however, her MIBG did not show evidence of an avid lesion. Flexible bronchoscopy disclosed compression of the RUL bronchus. Lung biopsy revealed findings consistent with follicular bronchiolitis, whereas lymph node biopsy showed reactive follicular and interfollicular hyperplasia. She was treated with IV steroids and did not have any recurrence. DISCUSSION: Notably, our patient has a complex chromosomal anomaly that does not typically present with pulmonary problems; however, deletions in chromosome 1p36 have been linked to reactive lymphoid hyperplasia and follicular lymphoma. FB is a rare disease in children. In adults, most cases are associated with collagen vascular diseases, immunodeficiency, or hypersensitivity reaction.1 This disease is characterized by bronchiolar narrowing by external compression due to lymphoid hyperplasia, which is seen in our patient.2 Affected children may present with tachypnea, respiratory distress and failure to thrive. Lung biopsy is necessary for confirmation of diagnosis. There are no well-established guidelines for the treatment of this condition, but macrolides and steroids have been suggested to have a benefit.3 Immunosuppressive agents are generally reserved for refractory cases. CONCLUSIONS: To our knowledge, this is the first case of FB reported on a child with chromosome 1p36 deletion. The etiology of this disease in children is unknown; however, diagnosis should be considered in a child with chronic bronchial obstruction. Reference #1: Yousem S.A., et al. Follicular bronchitis/bronchiolitis. Hum Pathol. 1985 Jul;16(7):700-706. Reference #2: Kinane B.T., et al. FB in the Pediatric Population. Chest. 1993; 104:1183-1186. Reference #3: Dias A., et al. FB: A Rare Cause of Persistent Atelectasis in Children. Respiratory Medicine Case Reports. 2013; 10:7-9. DISCLOSURE: The following authors have nothing to disclose: Marissa Love, Jane Taylor, Wendy Estrellado No Product/Research Disclosure Information

Essential Role of the Zinc Finger Transcription Factor Casz1 for Mammalian Cardiac Morphogenesis and Development

Chromosome 1p36 deletion syndrome is one of the most common terminal deletions observed in humans and is related to congenital heart disease (CHD). However, the 1p36 genes that contribute to heart disease have not been clearly delineated. Human CASZ1 gene localizes to 1p36 and encodes a zinc finger transcription factor. Casz1 is required for Xenopus heart ventral midline progenitor cell differentiation. Whether Casz1 plays a role during mammalian heart development is unknown. Our aim is to determine 1p36 gene CASZ1 function at regulating heart development in mammals. We generated a Casz1 knock-out mouse using Casz1-trapped embryonic stem cells. Casz1 deletion in mice resulted in abnormal heart development including hypoplasia of myocardium, ventricular septal defect, and disorganized morphology. Hypoplasia of myocardium was caused by decreased cardiomyocyte proliferation. Comparative genome-wide RNA transcriptome analysis of Casz1 depleted embryonic hearts identifies abnormal expression of genes that are critical for muscular system development and function, such as muscle contraction genes TNNI2, TNNT1, and CKM; contractile fiber gene ACTA1; and cardiac arrhythmia associated ion channel coding genes ABCC9 and CACNA1D. The transcriptional regulation of some of these genes by Casz1 was also found in cellular models. Our results showed that loss of Casz1 during mouse development led to heart defect including cardiac noncompaction and ventricular septal defect, which phenocopies 1p36 deletion syndrome related CHD. This suggests that CASZ1 is a novel 1p36 CHD gene and that the abnormal expression of cardiac morphogenesis and contraction genes induced by loss of Casz1 contributes to the heart defect.

Chromosome 1p36 Deletion Syndrome: Prenatal Diagnosis, Molecular Cytogenetic Characterization and Fetal Ultrasound Findings

To present prenatal diagnosis and molecular cytogenetic characterization of de novo partial monosomy 1p (1p36.23→pter) and partial trisomy 20p (20p12.1→pter) associated with ventriculomegaly, ventricular septal defect and midface hypoplasia. A 31-year-old, primigravid woman was referred for amniocentesis at 20 gestational weeks because of ventriculomegaly, ventricular septal defect, and midface hypoplasia. Amniocentesis revealed an aberrant derivative chromosome 1, or der(1). Parental karyotypes were normal. Spectral karyotyping analysis revealed that the der(1) contained a segment of chromosome 20 in the distal end of the short arm of chromosome 1. Array comparative genomic hybridization demonstrated an 8.4-Mb distal 1p deletion and a 14-Mb distal 20p duplication. The karyotype was 46,XX,der(1)t(1;20)(p36.23;p12.1)dn. Polymorphic DNA marker analysis determined the paternal origin of the aberrant chromosome. The pregnancy was subsequently terminated. A 462-g malformed female fetus was delivered at 22 gestational weeks with a prominent forehead, midface hypoplasia, a flat nasal bridge, low-set ears, a long philtrum, a pointed chin and micrognathia. Spectral karyotyping, fluorescence in situ hybridization and array comparative genomic hybridization are useful for the prenatal investigation of the nature of a de novo aberrant derivative chromosome. Partial monosomy 1p (1p36.23→pter) and partial trisomy 20p (20p12.1→pter) are associated with ventriculomegaly, ventricular septal defect and midface hypoplasia on prenatal ultrasound. Prenatal diagnosis of ventriculomegaly, congenital heart defects and midface hypoplasia should alert clinicians to chromosome 1p36 deletion syndrome and prompt molecular cytogenetic analysis if necessary.

Revisit on a distinctive chromosome 1p36 deletion syndrome: report of one case and review of the English literature

Terminal deletion of chromosome 1p, especially of the segment 1p36.3-1pter, is difficult to detect from cytogenetic G-banded karyotypes [1,2]. Since the intervention of the fluorescence in situ hybridization (FISH) study with a subtelomeric 1p probe, this terminal 1p36 deletion can be diagnosed with ascertainment. We have recently experienced a 6-month-old female infant, who was inborn with de novo terminal deletion of chromosome 1p, i.e., del (1)(p36.3-pter), incurring generalized motor hypotonia, failure-to-thrive, delayed developmental milestones, craniofacial dysmorphism, and a large patent ductus arteriosus. FISH study of the proband's blood documented a karyotype of 46,XX,del(1)(p36.3-pter), or 46,XX, 1ps de novo.ish 1ps (1psubtelomere-, D13Z1/D21Z1-, D14Z1/D22Z1-, D15Z1-). Cytogenetic and FISH studies of the parental chromosomes showed normal karyotypes. All these analyses indicate that this rearrangement of the proband's chromosome is de novo, rather than familial, in nature.

A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy

Chromosome 1p36 deletion syndrome is characterized by hypotonia, moderate to severe developmental and growth retardation, and characteristic craniofacial dysmorphism. Muscle hypotonia and delayed motor development are almost constant features of the syndrome. We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association may indicate that one of the CFTD loci is located at 1p36. Ski proto-oncogene -/- mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome. Because fluorescent in situ hybridization analysis revealed that the human SKI gene is deleted in our patient, some genes in 1p36, including SKI proto-oncogene, may be involved in muscle hypotonia and delayed motor development in this syndrome.