Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy: Insight from Trio Whole Genome Analysis and Isodisomy Mapping

An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS). Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular...

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Bibliographic Details
Published in:Genes 2024-07, Vol.15 (7), p.946
Main Authors: Cuk, Mario, Unal, Busra, Bevanda, Andjela, Hayes, Connor P, Walker, McKenzie, Abraamyan, Feruza, Beluzic, Robert, Gornik, Kristina Crkvenac, Ozretic, David, Prutki, Maja, Nie, Qian, Reddi, Honey V, Ghazani, Arezou A
Format: Article
Language:English
Subjects:
Age
Chromosome 15
Chromosomes
Congenital diseases
Creatine kinase
Creatinine
Development and progression
DNA methylation
Ethylenediaminetetraacetic acid
Etiology
Gene mapping
Genes
Genetic analysis
Genetic aspects
Genetic disorders
Genomes
Genomic analysis
Genomics
Genotype & phenotype
Hospitals
Joints
Kinases
Muscular dystrophy
Obesity
Pediatrics
Phenotypes
Prader-Willi syndrome
Serum levels
Uniparental disomy
Whole genome sequencing
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Summary:An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS). Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15, expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM#253600) in the same patient. This report highlights the utility of joint analysis and the need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotypes.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes15070946