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Exome sequencing study of partial agenesis of the corpus callosum in men with developmental delay, epilepsy, and microcephaly.

ABSTRACT: 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.

SUBMITTER: Meloche J

PROVIDER: S-EPMC6978259 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Exome sequencing study of partial agenesis of the corpus callosum in men with developmental delay, epilepsy, and microcephaly.

Meloche Jolyane J Brunet Vanessa V Gagnon Pierre-Alexandre PA Lavoie Marie-Ève MÈ Bouchard Jean-Benoît JB Nadaf Javad J Majewski Jacek J Morin Charles C Laprise Catherine C

Molecular genetics & genomic medicine 20191002 1

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Single-nucleotide v ...[more]

PMID: 31578829

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Project description:BackgroundImpaired social functioning is a common symptom of individuals with developmental disruptions in callosal connectivity. Among these developmental conditions, agenesis of the corpus callosum provides the most extreme and clearly identifiable example of callosal disconnection. To date, deficits in nonliteral language comprehension, humor, theory of mind, and social reasoning have been documented in agenesis of the corpus callosum. Here, we examined a basic social ability as yet not investigated in this population: recognition of facial emotion and its association with social gaze.MethodsNine individuals with callosal agenesis and nine matched controls completed four tasks involving emotional faces: emotion recognition from upright and inverted faces, gender recognition, and passive viewing. Eye-tracking data were collected concurrently on all four tasks and analyzed according to designated facial regions of interest.ResultsIndividuals with callosal agenesis exhibited impairments in recognizing emotions from upright faces, in particular lower accuracy for fear and anger, and these impairments were directly associated with diminished attention to the eye region. The callosal agenesis group exhibited greater consistency in emotion recognition across conditions (upright vs. inverted), with poorest performance for fear identification in both conditions. The callosal agenesis group also had atypical facial scanning (lower fractional dwell time in the eye region) during gender naming and passive viewing of faces, but they did not differ from controls on gender naming performance. The pattern of results did not differ when taking into account full-scale intelligence quotient or presence of autism spectrum symptoms.ConclusionsAgenesis of the corpus callosum results in a pattern of atypical facial scanning characterized by diminished attention to the eyes. This pattern suggests that reduced callosal connectivity may contribute to the development and maintenance of emotion processing deficits involving reduced attention to others' eyes.

Dataset Information

Exome sequencing study of partial agenesis of the corpus callosum in men with developmental delay, epilepsy, and microcephaly.

Publications

Exome sequencing study of partial agenesis of the corpus callosum in men with developmental delay, epilepsy, and microcephaly.

Similar Datasets

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