TY - JOUR
T1 - Optical Genome Mapping (OGM) Identifies Multiple Structural Variants in a Case With Atypical Phelan-McDermid Syndrome
AU - Macke, Erica L.
AU - Miller, Anthony R.
AU - Colwell, Caitlyn M.
AU - Gonzalez, Maria Hernandez
AU - Hunter, Jesse
AU - Venkata, Lakshmi Prakruthi Rao
AU - Walker, Lauren
AU - Wheeler, Gregory
AU - Wilson, Richard K.
AU - Mardis, Elaine R.
AU - Miller, Katherine E.
AU - Mathew, Mariam T.
AU - Chaudhari, Bimal P.
AU - Akkari, Yassmine
N1 - Publisher Copyright:
© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
PY - 2025/3
Y1 - 2025/3
N2 - Here we describe a neonate exhibiting hypotonia, macrocephaly, renal cysts, and respiratory failure requiring tracheostomy and ventilator support. Genetic analysis via rapid genome sequencing (rGS) identified a loss on chromosome 4 encompassing polycystin-2 (PKD2) and a loss on chromosome 22 encompassing SH3 and Multiple Ankyrin Repeat Domains 3 (SHANK3), indicative of Phelan-McDermid syndrome. Further analysis via traditional karyotyping, Optical Genome Mapping (OGM), and PacBio long-read sequencing revealed a more complex landscape of chromosomal rearrangements in this individual, including a balanced 3;12 translocation, and an unbalanced 17;22 translocation. The proband's phenotypic presentation is thought to be the result of Phelan-McDermid syndrome and represents an expansion of the described phenotypes to include significant respiratory failure. This study underscores the challenges and importance of comprehensive genetic testing in elucidating complex presentations and highlights the need for complementary testing methods to overcome limitations in resolution.
AB - Here we describe a neonate exhibiting hypotonia, macrocephaly, renal cysts, and respiratory failure requiring tracheostomy and ventilator support. Genetic analysis via rapid genome sequencing (rGS) identified a loss on chromosome 4 encompassing polycystin-2 (PKD2) and a loss on chromosome 22 encompassing SH3 and Multiple Ankyrin Repeat Domains 3 (SHANK3), indicative of Phelan-McDermid syndrome. Further analysis via traditional karyotyping, Optical Genome Mapping (OGM), and PacBio long-read sequencing revealed a more complex landscape of chromosomal rearrangements in this individual, including a balanced 3;12 translocation, and an unbalanced 17;22 translocation. The proband's phenotypic presentation is thought to be the result of Phelan-McDermid syndrome and represents an expansion of the described phenotypes to include significant respiratory failure. This study underscores the challenges and importance of comprehensive genetic testing in elucidating complex presentations and highlights the need for complementary testing methods to overcome limitations in resolution.
KW - long-read Sequencing
KW - optical Genome Mapping
KW - Phelan-McDermid Syndrome
KW - rapid Genome Sequencing
UR - https://www.scopus.com/pages/publications/85208939850
U2 - 10.1002/ajmg.a.63929
DO - 10.1002/ajmg.a.63929
M3 - Article
C2 - 39535355
AN - SCOPUS:85208939850
SN - 1552-4825
VL - 197
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 3
M1 - e63929
ER -