1p microdeletion in sibs with minimal phenotypic manifestations

Martínez, José Enrique; Tuck‐Muller, Cathy M.; Gasparrini, William; Li, Shibo; Wertelecki, Wladimir

doi:10.1002/(sici)1096-8628(19990115)82:2<107::aid-ajmg1>3.0.co;2-n

Cited by 9 publications

(5 citation statements)

References 6 publications

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“…The male presented with delayed development, growth failure, microcephaly, low-set ears, narrow palpebral fissures, high arched palate, cryptorchidism, hypertrichosis, and pulmonary atresia with a ventricular septal defect. Remarkably, two siblings reported by Martinez et al, 12 with a paracentric inversion 1p22.3p34.1 and a larger deletion 1p34.1p34.3 than in our patient, did not have multiple malformations and delayed development.…”

Section: Discussionsupporting

confidence: 46%

A novel microdeletion in 1(p34.2p34.3), involving the SLC2A1 (GLUT1) gene, and severe delayed development

Vermeer

Koolen

Visser

et al. 2007

Develop Med Child Neuro

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A de novo 4.1‐megabase microdeletion of chromosome 1p34.2p34.3 has been identified by array‐based comparative genomic hybridization in a young male with severely delayed development, microcephaly, pronounced hypotonia, and facial dysmorphism. The deleted region encompasses 48 genes, among them the glucose transporter 1 (SLC2A1 or GLUT1) gene. The deletion of the GLUT1 gene was in line with the abnormal ratio of cerebrospinal fluid (CSF) glucose to blood glucose, indicative of GLUT1 deficiency syndrome (MIM #606777). GLUT1 deficiency syndrome is characterized by therapy‐resistant infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and a low concentration of glucose in the CSF. It is known that a ketogenic diet can lead to better control of seizures. This case study shows that identifying a microdeletion as the cause of learning disability is not only important for genetic counselling but might also lead to therapeutic intervention.

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Section: Discussionsupporting

confidence: 46%

A novel microdeletion in 1(p34.2p34.3), involving the SLC2A1 (GLUT1) gene, and severe delayed development

Vermeer

Koolen

Visser

et al. 2007

Develop Med Child Neuro

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“… Karyotyping 9 del(1)(p34.1p34.3) [ 8 ] a 1999 Pt 1 Severe learning disability, attention deficit disorder (ADD), craniofacial anomalies. Karyotyping and FISH with probes specific for chromosome 1 (COATA-SOME TM 1, p5205-DG.5) 10 del(1)(p34.1p34.3) [ 8 ] a 1999 Pt 2 Attention deficit hyperactivity disorder (ADHD), craniofacial anomalies, disturbed behaviors. Karyotyping and FISH with probes specific for chromosome 1 (COATA SOME TM 1, p5205-DG.5) 11 del(1)(p32.1p32.3) [ 9 ] a 2002 Pt 1 Global developmental delay, craniofacial anomalies, absence of corpus callosum, type I Chiari malformation, tethered cord.…”

Section: Introductionmentioning

confidence: 99%

Comparative deletion mapping at 1p31.3-p32.2 implies NFIA responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability

et al. 2016

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BackgroundWhile chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microdeletions in the short arm have been documented. More than half of the 1p microdeletion cases were reported in the pre-microarray era and as a result, the proximal and distal boundaries containing the exact number of genes involved in the microdeletions have not been clearly defined.ResultsWe revisited a previous case of a 10-year old female patient with a 1p32.1p32.3 microdeletion displaying syndromic intellectual disability. We performed microarray analysis as well as qPCR to define the proximal and distal deletion breakpoints and revised the karyotype from 1p32.1p32.3 to 1p31.3p32.2. The deleted chromosomal region contains at least 35 genes including NFIA. Comparative deletion mapping shows that this region can be dissected into five chromosomal segments containing at least six candidate genes (DAB1, HOOK1, NFIA, DOCK7, DNAJC6, and PDE4B) most likely responsible for syndromic intellectual disability, which was corroborated by their reduced transcript levels in RT-qPCR. Importantly, one patient with an intragenic microdeletion within NFIA and an additional patient with a balanced translocation disrupting NFIA display intellectual disability coupled with macrocephaly.ConclusionWe propose NFIA is responsible for intellectual disability coupled with macrocephaly, and microdeletions at 1p31.3p32.2 constitute a contiguous gene syndrome with several genes contributing to syndromic intellectual disability.

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“…One boy with a much larger ∼17 Mb visible deletion had severe developmental delay, poor growth, and microcephaly 36. Two sibs who inherited a juxtaposed inversion (inv 1p22.3p34.1) and deletion (1p34.1p34.3) of this region presented with behaviour disorders, although their intelligence and appearance were normal 37. A detailed genotype–phenotype analysis involving 1p34.2p34.3 in these patients is provided in the supplementary materials.…”

Section: Discussionmentioning

confidence: 99%

A de novo 1p34.2 microdeletion identifies the synaptic vesicle gene RIMS3 as a novel candidate for autism

Kumar

Sudi

Babatz

et al. 2009

Journal of Medical Genetics

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BackgroundA child with autism and mild microcephaly was found to have a de novo 3.3 Mb microdeletion on chromosome 1p34.2p34.3. The hypothesis is tested that this microdeletion contains one or more genes that underlie the autism phenotype in this child and in other children with autism spectrum disorders.MethodsTo search for submicroscopic chromosomal rearrangements in the child, array comparative genomic hybridisation (aCGH) was performed using a 19 K whole genome human bacterial artificial chromosome (BAC) array and the Illumina 610-Quad BeadChip microarray. Ingenuity pathway analysis (IPA) was used to construct functional biological networks to identify candidate autism genes. To identify putative functional variants in candidate genes, mutation screening was performed using polymerase chain reaction (PCR) based Sanger sequencing in 512 unrelated autism patients and 462 control subjects.ResultsA de novo 3.3 Mb deletion containing ∼43 genes in chromosome 1p34.2p34.3 was identified and subsequently confirmed using fluorescence in situ hybridization (FISH). Literature review and bioinformatics analyses identified Regulating Synaptic Membrane Exocytosis 3 (RIMS3) as the most promising autism candidate gene. Mutation screening of this gene in autism patients identified five inherited coding variants, including one (p.E177A) that segregated with the autism phenotype in a sibship, was predicted to be deleterious, and was absent in 1161 controls.ConclusionsThis case report and mutation screening data suggest that RIMS3 is an autism causative or contributory gene. Functional studies of RIMS3 variants such as p.E177A should provide additional insight into the role of synaptic proteins in the pathophysiology of autism.

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1p microdeletion in sibs with minimal phenotypic manifestations

Cited by 9 publications

References 6 publications

A novel microdeletion in 1(p34.2p34.3), involving the SLC2A1 (GLUT1) gene, and severe delayed development

A novel microdeletion in 1(p34.2p34.3), involving the SLC2A1 (GLUT1) gene, and severe delayed development

Comparative deletion mapping at 1p31.3-p32.2 implies NFIA responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability

A de novo 1p34.2 microdeletion identifies the synaptic vesicle gene RIMS3 as a novel candidate for autism

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