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

Cuk, Mario; Unal, Busra; Bevanda, Andjela; Hayes, Connor P.; Walker, McKenzie; Abraamyan, Feruza; Belužić, Robert; Crkvenac Gornik, Kristina; Ozretic, David; Prutki, Maja; Nie, Qian; Reddi, Honey V.; Ghazani, Arezou A. (2024) Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy: Insight from Trio Whole Genome Analysis and Isodisomy Mapping. Genes, 15 (7). ISSN 2073-4425

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Abstract

Purpose: 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). Methods: 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: 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. Conclusion: 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.

Item Type:	Article
Uncontrolled Keywords:	joint WGS analysis; uniparental disomy; isodisomy; heterodisomy; Prader-Willi syndrome; calpainopathy
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Human Genetics, Genomics and Proteomics
Divisions:	Division of Molecular Medicine
Depositing User:	Ivana Vuglec
Date Deposited:	13 Oct 2025 08:33
URI:	http://fulir.irb.hr/id/eprint/9990
DOI:	10.3390/genes15070946

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