Open AccessExome sequencing study of partial agenesis of the corpus callosum in men with developmental delay, epilepsy, and microcephaly
Author(s) -
Meloche Jolyane,
Brunet Vanessa,
Gag PierreAlexandre,
Lavoie MarieÈve,
Bouchard JeanBenoît,
Nadaf Javad,
Majewski Jacek,
Morin Charles,
Laprise Catherine
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.992
Subject(s) - exome sequencing , microcephaly , genetics , biology , frameshift mutation , epilepsy , exome , missense mutation , agenesis of the corpus callosum , corpus callosum , proband , phenotype , mutation , gene , anatomy , neuroscience
Background This study reports the genetic features of four Caucasian males from the Saguenay‒Lac‐St‐Jean region affected by partial agenesis of the corpus callosum (ACC) with hypotonia, epilepsy, developmental delay, microcephaly, hypoplasia, and autistic behavior. Methods We performed whole exome sequencing (WES) to identify new genes involved in this pathological phenotype. The regions of interest were subsequently sequenced for family members. Results Single‐nucleotide variations (SNVs) and insertions or deletions were detected in genes potentially implicated in brain defects observed in these patients. One patient did not have mutations in genes related to ACC, but carried a de novo pathogenic mutation in Mucolipin‐1 ( MCOLN1 ) and was diagnosed with mucolipidosis type IV. Among the other probands, missense SNVs were observed in DCLK2 (Doublecortin Like Kinase 2), HERC2 (HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 2), and KCNH3 (Potassium channel, voltage‐gated, subfamily H, member 3). One patient also carried a non‐frameshift insertion in CACNA1A (Cav2.1(P/Q‐type) calcium channels). Conclusion Although no common genetic defect was observed in this study, we provide evidence for new avenues of investigation for ACC, such as molecular pathways involving HERC2 , CACNA1A , KCNH3, and more importantly DCLK2 . We also allowed to diagnose an individual with mucolipidosis type IV.