A rare case of complete uniparental isodisomy of chromosome 2 with no phenotypic abnormalities

Achromatopsia (ACHM) is a rare autosomal recessively inherited retinal disease characterized by congenital photophobia, nystagmus, low visual acuity, and absence of color vision. ACHM is genetically heterogeneous and can be caused by biallelic mutations in the genes CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, or ATF6. We undertook molecular genetic analysis in a single female patient with a clinical diagnosis of ACHM and identified the homozygous variant c.778G>C;p.(D260H) in the CNGA3 gene. While segregation analysis in the father, as expected, identified the CNGA3 variant in a heterozygous state, it could not be displayed in the mother. Microsatellite marker analysis provided evidence that the homozygosity of the CNGA3 variant is due to partial or complete paternal uniparental isodisomy (UPD) of chromosome 2 in the patient. Apart from the ACHM phenotype, the patient was clinically unsuspicious and healthy. This is one of few examples proving UPD as the underlying mechanism for the clinical manifestation of a recessive mutation in a patient with inherited retinal disease. It also highlights the importance of segregation analysis in both parents of a given patient or especially in cases of homozygous recessive mutations, as UPD has significant implications for genetic counseling with a very low recurrence risk assessment in such families.

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A rare case of uniparental isodisomy of chromosome 19 with no phenotypic abnormalities

Taiwanese Journal of Obstetrics and Gynecology ◽

10.1016/j.tjog.2021.01.023 ◽

2021 ◽

Vol 60 (2) ◽

pp. 376-377

Author(s):

Jieping Song ◽

Ling Zhu ◽

Ting Zhou ◽

Bo Wang

Keyword(s):

Rare Case ◽

Chromosome 19 ◽

Uniparental Isodisomy

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Uniparental isodisomy of chromosome 2 causing MRPL44-related multisystem mitochondrial disease

Molecular Biology Reports ◽

10.1007/s11033-021-06188-1 ◽

2021 ◽

Vol 48 (3) ◽

pp. 2093-2104

Author(s):

Alejandro Horga ◽

Andreea Manole ◽

Alice L. Mitchell ◽

Enrico Bugiardini ◽

Iain P. Hargreaves ◽

...

Keyword(s):

Mitochondrial Disease ◽

Chromosome 2 ◽

Uniparental Isodisomy

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A Case of Sporadic Pseudohypoparathyroidism Type 1B Presented with Hypokalemia

Hormone and Metabolic Research ◽

10.1055/a-1528-7471 ◽

2021 ◽

Author(s):

Wen-jun Yang ◽

Qin Zhang ◽

Ping Jin

Keyword(s):

Parathyroid Hormone ◽

Rare Case ◽

Autosomal Dominant ◽

Molecular Level ◽

Differentially Methylated Regions ◽

Uniparental Isodisomy

Dear EditorLuo et al. 1 reported two cases of autosomal dominant pseudohypoparathyroidism type 1B (AD-PHP1B) and reviewed literature about the genetic and epigenetic characteristics of AD-PHP1B. Pseudohypoparathyroidism (PHP) is a cluster of heterogeneous diseases characterized by hypocalcemia and hyperphosphatemia due to resistance to parathyroid hormone (PTH). PHP1B almost results from methylation abnormalities of the maternal differentially methylated regions (DMRs) and can be divided into sporadic PHP1B and AD-PHP1B 1. As mentioned in this article 1, AD-PHP1B is caused by heterozygous maternal deletions within GNAS or STX16, which are associated with loss of methylation at the A/B DMR alone or at all maternally methylated GNAS exons. While sporadic PHP1B remains unclear at the molecular level, except for approximately 10% of the patients caused by paternal uniparental isodisomy or heterodisomy involving chromosome 20q (patUPD20q) 2. Here, we would like to present a rare case of sporadic PHP1B occurring in association with hypokalemia.

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A patient with Silver-Russell syndrome with multilocus imprinting disturbance, and Schimke immuno-osseous dysplasia unmasked by uniparental isodisomy of chromosome 2

Journal of Human Genetics ◽

10.1038/s10038-021-00937-7 ◽

2021 ◽

Author(s):

Kaori Hara-Isono ◽

Keiko Matsubara ◽

Riku Hamada ◽

Shun Shimada ◽

Tomomi Yamaguchi ◽

...

Keyword(s):

Chromosome 2 ◽

Osseous Dysplasia ◽

Uniparental Isodisomy ◽

Silver Russell Syndrome

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Warburg Micro Syndrome 1 due to Segmental Paternal Uniparental Isodisomy of Chromosome 2 Detected by Whole-Exome Sequencing and Homozygosity Mapping

Cytogenetic and Genome Research ◽

10.1159/000509214 ◽

2020 ◽

Vol 160 (6) ◽

pp. 309-315

Author(s):

Abdullah Sezer ◽

Gülsüm Kayhan ◽

Altuğ Koç ◽

Mehmet A. Ergün ◽

Ferda E. Perçin

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Uniparental Disomy ◽

Homozygosity Mapping ◽

Spastic Diplegia ◽

Chromosome 2 ◽

Whole Exome ◽

Uniparental Isodisomy ◽

Mapping Analysis ◽

Warburg Micro Syndrome

Warburg micro syndrome (WARBM) is a rare autosomal recessive disorder characterized by microcephaly, cortical dysplasia, intellectual disability, ocular abnormalities, spastic diplegia, and microgenitalia. WARBM has 4 subtypes arising from pathogenic variants in 4 genes (RAB18, RAB3GAP1, RAB3GAP2, and TBC1D20). Here, we report on a patient with a homozygous pathogenic c.665delC (p.Pro222HisfsTer30) variant in the RAB3GAP1 gene identified by whole-exome sequencing (WES) analyses. Only his father was a heterozygous carrier, and homozygosity mapping analysis of the WES data revealed large loss-of-heterozygosity regions in both arms of chromosome 2, interpreted as uniparental isodisomy. This uniparental disomy pattern could be due to paternal meiosis I nondisjunction because of the preserved heterozygosity in the pericentromeric region. This report provides novel insights, including a rare form of UPD, usage of homozygosity mapping analysis for the evaluation of isodisomy, and the first reported case of WARBM1 as a result of uniparental isodisomy.

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