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Title: De Novo PORCN and ZIC2 mutations in a highly consanguineous family
Author: Castilla Vallmanya, Laura
Gürsoy, Semra
Giray Bozkaya, Özlem
Prat Planas, Aina
Bullich, Gemma
Matalonga Borrel, Lesley
Centeno Pla, Mónica
Rabionet Janssen, Raquel
Grinberg Vaisman, Daniel Raúl
Balcells Comas, Susana
Urreizti, Roser
Keywords: Genètica del desenvolupament
Lesions cerebrals
Developmental genetics
Brain damage
Issue Date: 4-Feb-2021
Publisher: MDPI
Abstract: We present a Turkish family with two cousins (OC15 and OC15b) affected with syndromic developmental delay, microcephaly, and trigonocephaly but with some phenotypic traits distinct between them. OC15 showed asymmetrical skeletal defects and syndactyly, while OC15b presented with a more severe microcephaly and semilobal holoprosencephaly. All four progenitors were related and OC15 parents were consanguineous. Whole Exome Sequencing (WES) analysis was performed on patient OC15 as a singleton and on the OC15b trio. Selected variants were validated by Sanger sequencing. We did not identify any shared variant that could be associated with the disease. Instead, each patient presented a de novo heterozygous variant in a different gene. OC15 carried a nonsense mutation (p.Arg95*) in PORCN, which is a gene responsible for Goltz-Gorlin syndrome, while OC15b carried an indel mutation in ZIC2 leading to the substitution of three residues by a proline (p.His404_Ser406delinsPro). Autosomal dominant mutations in ZIC2 have been associated with holoprosencephaly 5. Both variants are absent in the general population and are predicted to be pathogenic. These two de novo heterozygous variants identified in the two patients seem to explain the major phenotypic alterations of each particular case, instead of a homozygous variant that would be expected by the underlying consanguinity.
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It is part of: International Journal of Molecular Sciences, 2021, vol. 22(4), num. 1549
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ISSN: 1661-6596
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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