Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy Using Uniparental Disomy and Joint Whole Genome Analysis

Mario Cuk
,
Busra Unal
ORCID logo ,
Andjela Bevanda
,
Connor P Hayes
,
McKenzie Walker
,
Feruza Abraamyan
,
Robert Belužić
,
Kristina Crkvenac Gornik
,
David Ozretic
,
Maja Prutki
,
Qian Nie
,
Honey V. Reddi
,
Arezou A. Ghazani
* ORCID logo
Version 1 : Received: 20 June 2024 / Approved: 20 June 2024 / Online: 21 June 2024 (10:22:17 CEST)

How to cite: Cuk, M.; Unal, B.; Bevanda, A.; Hayes, C. P.; Walker, M.; Abraamyan, F.; Belužić, R.; Crkvenac Gornik, K.; Ozretic, D.; Prutki, M.; Nie, Q.; Reddi, H. V.; Ghazani, A. A. Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy Using Uniparental Disomy and Joint Whole Genome Analysis. Preprints 2024, 2024061485. https://doi.org/10.20944/preprints202406.1485.v1 Cuk, M.; Unal, B.; Bevanda, A.; Hayes, C. P.; Walker, M.; Abraamyan, F.; Belužić, R.; Crkvenac Gornik, K.; Ozretic, D.; Prutki, M.; Nie, Q.; Reddi, H. V.; Ghazani, A. A. Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy Using Uniparental Disomy and Joint Whole Genome Analysis. Preprints 2024, 2024061485. https://doi.org/10.20944/preprints202406.1485.v1

Abstract

Purpose: 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 need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotype.

Keywords

Joint-WGS analysis; Uniparental Disomy; Isodisomy; Heterodisomy; Prader-Willi Syndrome; Calpainopathy

Subject

Biology and Life Sciences, Other

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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