Genomic and phenotypic delineation of congenital microcephaly

Katta, Girisha M (2018) Genomic and phenotypic delineation of congenital microcephaly. Genetics In Medicine. pp. 1-8. ISSN 1098-3600

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Abstract

Purpose: Congenital microcephaly (CM) is an important birth defect with long term neurological sequelae. We aimed to perform detailed phenotypic and genomic analysis of patients with Mendelian forms of CM.Methods: Clinical phenotyping, targeted or exome sequencing,and autozygome analysis.Results: We describe 150 patients (104 families) with 56 Mendelian forms of CM. Our data show little overlap with the genetic causes of postnatal microcephaly. We also show that a broad definition of primary microcephaly —as an autosomal recessive form of nonsyndromic CM with severe postnatal deceleration of occipitofrontal circumference—is highly sensitive but has a limited specificity. In addition, we expand the overlap between primary microcephaly and microcephalic primordial dwarfism both clinically (short stature in >52% of patients with primary microcephaly) and molecularly (e.g., we report the first instance of CEP135-related microcephalic primordial dwarfism).We expand the allelic and locus heterogeneity of CM by reporting 37 novel likely disease-causing variants in 27 disease genes,confirming the candidacy of ANKLE2, YARS, FRMD4A, and THG1L, and proposing the candidacy of BPTF, MAP1B, CCNH,and PPFIBP1.Conclusion: Our study refines the phenotype of CM, expands its genetics heterogeneity, and informs the workup of children born with this developmental brain defect.

Item Type: Article
Uncontrolled Keywords: Autozygome; Primary microcephaly; Dwarfism; CNTRL
Subjects: Medicine > KMC Manipal > Obstetrics & Gynaecology
Depositing User: KMC Library
Date Deposited: 10 Jan 2019 07:07
Last Modified: 10 Jan 2019 07:07
URI: http://eprints.manipal.edu/id/eprint/152865

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