Molecular prenatal diagnosis of a sporadic alobar holoprosencephalic fetus: genotype-phenotype correlations

Gekas, Jean and Sergi, Consolato and Kamnasaran, Deepak (2012) Molecular prenatal diagnosis of a sporadic alobar holoprosencephalic fetus: genotype-phenotype correlations. Journal of prenatal medicine, 6 (3). pp. 36-39. ISSN 1971-3290

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Objective: holoprosencephaly is the most common forebrain malformation syndrome with a multifactorial etiology. Currently, mutations are identified in 5-10% of non syndromic, non-chromosomal cases in at least 12 genes. We report the molecular prenatal diagnosis of a fetus with alobar holoprosencephaly. Methods: CTG band karyotyping and array CGH genome-wide cytogenetic screenings were done, in conjunction with DNA sequence analyses of the SHH, ZIC2, SIX3 and TGIF genes in search of a molecular etiology and with comparison of findings to prior cases. Results: standard CTG band karyotyping and array CGH genome-wide screening failed to identify plausible chromosome imbalances or structural anomalies. However, extensive sequencing of the genomic DNA from the fetus and both parents on all exon and exon-intron boundaries of the four most commonly mutated genes: SHH, ZIC2, SIX3 and TGIF, identified codon 100 of the sonic hedgehog (SHH) gene having a hotspot for loss-of-function mutations in our case and others. Conclusion: mutations in codon 100 of SHH were discovered in both sporadic and autosomal dominant inherited cases with evidence of variable expressivity and penetrance. Collectively, this study reinforces the complexity of genotype-phenotype correlations in the prenatal diagnosis of holoprosencephalic fetuses.

Item Type: Article
Uncontrolled Keywords: Genetic testing, pregnancy, craniofacial dysmorphology, birth defect, genetic counseling
Subjects: 600 Tecnologia - Scienze applicate > 610 Medicina e salute (Classificare qui la tecnologia dei servizi medici) > 618 Altri rami della medicina; Ginecologia e ostetricia, Pediatria, Geriatria > 618.3 Malattie e complicazioni della gravidanza
Depositing User: Gianni Aiello
Date Deposited: 29 May 2013 11:51
Last Modified: 10 Apr 2014 08:34

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