Paternal uniparental isodisomy of chromosome 22 in a patient with metachromatic leukodystrophy

Niida, Yo; Kuroda, Masashi; Mitani, Yusuke; Yokoi, Ayano; Ozaki, Mamoru

doi:10.1038/jhg.2012.97

Cited by 11 publications

(7 citation statements)

References 15 publications

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“…His father and sister were detected as carriers of this gene, while his mother did not have mutated allele. [ 22 ] Therefore, this patient developed the disease by uniparental isodisomy. But all of these 3 cases are different from our case, as they are all diagnosed in adulthood, while our case was diagnosed prenatally.…”

Section: Discussionmentioning

confidence: 97%

“…To our knowledge, there have been only 3 cases of paternal UPD 22 reported (Table 1 ), [ 20 – 22 ] two of them phenotypically normal, and both of them and their father have robertsonian translocation. [ 20 , 21 ] The third one had metachromatic leukodystrophy, [ 22 ] which is an autosomal recessive disease caused by defects of a protein coding gene ARSA (OMIM ID: ∗ 607574). His father and sister were detected as carriers of this gene, while his mother did not have mutated allele.…”

Section: Discussionmentioning

confidence: 99%

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Uniparental disomy and prenatal phenotype

Liu²,

Song³

et al. 2017

Medicine

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Rationale:Uniparental disomy (UPD) gives a description of the inheritance of both homologues of a chromosome pair from the same parent. The consequences of UPD depend on the specific chromosome/segment involved and its parental origin.Patient concerns:We report prenatal phenotypes of 2 rare cases of UPD.Diagnoses:The prenatal phenotype of case 1 included sonographic markers such as enlarged nuchal translucency (NT), absent nasal bone, short femur and humerus length, and several structural malformations involving Dandy–Walker malformation and congenital heart defects. The prenatal phenotype of Case 2 are sonographic markers, including enlarged NT, thickened nuchal fold, ascites, and polyhydramnios without apparent structural malformations.Interventions:Conventional G-band karyotype appears normal in case 1, while it shows normal chromosomes with a small supernumerary marker chromosome (sSMC) in case 2. Genetic etiology was left unknown until single-nucleotide polymorphism-based array (SNP-array) was performed, and segmental paternal UPD 22 was identified in case 1 and segmental paternal UPD 14 was found in case 2.Outcomes:The parents of case 1 chose termination of pregnancy. The neonate of case 2 was born prematurely with a bellshaped small thorax and died within a day.Lessons:UPD cases are rare and the phenotypes are different, which depend on the origin and affected chromosomal part. If a fetus shows multiple anomalies that cannot be attributed to a common aneuploidy or a genetic syndrome, or manifests some features possibly related to an UPD syndrome, such as detection of sSMC, SNP-array should be considered.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Uniparental disomy and prenatal phenotype

Liu²,

Song³

et al. 2017

Medicine

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“…Homozygous mutation due to paternal UPD of chromosome22 had been reported in a metachromatic leukoencephalopathy (MLD) patient. In this study, we identified the first patient with MLC caused by maternal UPD of chromosome 22[ 25 ]. There was 25% risk of recurrence in the MLC families with regular autosomal recessive inheritance.…”

Section: Discussionmentioning

confidence: 99%

Ten Novel Mutations in Chinese Patients with Megalencephalic Leukoencephalopathy with Subcortical Cysts and a Long-Term Follow-Up Research

et al. 2016

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ObjectiveMegalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIM 604004) is a rare neurological deterioration disease. We aimed to clarify clinical and genetic features of Chinese MLC patients.MethodsClinical information and peripheral venous blood of 20 patients and their families were collected, Sanger-sequencing and Multiple Ligation-dependent Probe Amplification were performed to make genetic analysis. Splicing-site mutation was confirmed with RT-PCR. UPD was detected by haplotype analysis. Follow-up study was performed through telephone for 27 patients.ResultsOut of 20 patients, macrocephaly, classic MRI features, motor development delay and cognitive impairment were detected in 20(100%), 20(100%), 17(85%) and 4(20%) patients, respectively. 20(100%) were clinically diagnosed with MLC. 19(95%) were genetically diagnosed with 10 novel mutations in MLC1, MLC1 and GlialCAM mutations were identified in 15 and 4 patients, respectively. Deletion mutation from exon4 to exon9 and a homozygous point mutation due to maternal UPD of chromosome22 in MLC1 were found firstly. c.598-2A>C in MLC1 leads to the skip of exon8. c.772-1G>C in MLC1 accounting for 15.5%(9/58) alleles in Chinese patients might be a founder or a hot-spot mutation. Out of 27 patients in the follow-up study, head circumference was ranged from 56cm to 61cm in patients older than 5yeas old, with a median of 57cm. Motor development delay and cognitive impairment were detected in 22(81.5%) and 5(18.5%) patients, respectively. Motor and cognitive deterioration was found in 5 (18.5%) and 2 patients (7.4%), respectively. Improvements and MRI recovery were first found in Chinese patients. Rate of seizures (45.5%), transient motor retrogress (45.5%) and unconsciousness (13.6%) after head trauma was much higher than that after fever (18.2%, 9.1%, 0%, respectively).SignificanceIt’s a clinical and genetic analysis and a follow-up study for largest sample of Chinese MLC patients, identifying 10 novel mutations, expanding mutation spectrums and discovering clinical features of Chinese MLC patients.

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“…In our own experience, we encounter AR diseases caused by UPiD every 2-3 years [Niida et al, 2012b[Niida et al, , 2016. We test various AR diseases, and approximately 10-15 tests are performed per year.…”

Section: Discussionmentioning

confidence: 99%

Classification of Uniparental Isodisomy Patterns That Cause Autosomal Recessive Disorders: Proposed Mechanisms of Different Proportions and Parental Origin in Each Pattern

Niida

Ozaki

Shimizu

et al. 2018

Cytogenet Genome Res

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Patients with autosomal recessive (AR) disorders are usually born to parents both of whom are heterozygous carriers of the disease. However, in some instances only one of the parents is a carrier and a mutation is segregated to the patient through uniparental isodisomy (UPiD). Recently, an increasing number of such case reports has been published, and it has become clear that there are several different UPiD patterns that cause AR disorders. In this article, we report 3 remarkable patients with different patterns of UPiD. We then review 85 cases collected in the literature. We realized that they can be classified into 3 patterns: UPiD of the whole chromosome, segmental UPiD with uniparental heterodisomy (UPhD), and segmental UPiD caused by post-zygotic mitotic recombination (MiRe). Whole chromosomal UPiD accounted for the majority of cases, with paternal origin accounting for approximately twice as many cases as maternal origin. Most cases of segmental UPiD with UPhD were of maternal origin, with a dominancy of nondisjunction in meiosis I, while segmental UPiD through MiRe is the smallest pattern with equal parental origin. These differences in proportion and parental origin in each pattern can be explained by considering nondisjunction during oogenesis as the starting point and UPiD as subsequent events.

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Paternal uniparental isodisomy of chromosome 22 in a patient with metachromatic leukodystrophy

Cited by 11 publications

References 15 publications

Uniparental disomy and prenatal phenotype

Uniparental disomy and prenatal phenotype

Ten Novel Mutations in Chinese Patients with Megalencephalic Leukoencephalopathy with Subcortical Cysts and a Long-Term Follow-Up Research

Classification of Uniparental Isodisomy Patterns That Cause Autosomal Recessive Disorders: Proposed Mechanisms of Different Proportions and Parental Origin in Each Pattern

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