Holoprosencephaly, orofacial cleft, and frontonaso‐orbital encephaloceles: Genetic evaluation of a possible new syndrome
| العنوان: | Holoprosencephaly, orofacial cleft, and frontonaso‐orbital encephaloceles: Genetic evaluation of a possible new syndrome |
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| المؤلفون: | Fernanda Sarquis Jehee, Madelief Overes, Siulan Vendramini-Pittoli, Cristiano Tonello, Rejane A.C. Monteiro, Roseli Maria Zechi-Ceide, Juliana F. Mazzeu, Roza Ali-Amin, Nancy Mizue Kokitsu-Nakata, Antonio Richieri-Costa, Rosana Maria Candido-Souza, Lies H. Hoefsloot, Marjon van Slegtenhorst, Mariana Lacerda de Freitas |
| المساهمون: | Clinical Genetics |
| المصدر: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP American Journal of Medical Genetics Part A. Wiley-Liss Inc. |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Pathology, medicine.medical_specialty, ANORMALIDADES CRANIOFACIAIS, Oral cleft, business.industry, 030105 genetics & heredity, Semilobar holoprosencephaly, medicine.disease, Encephalocele, 03 medical and health sciences, 030104 developmental biology, Holoprosencephaly, Bilateral cleft lip, Genetics, medicine, Craniofacial, Agenesis of the corpus callosum, business, Genetics (clinical), Exome sequencing |
| الوصف: | Here we report on a Brazilian child who presented semilobar holoprosencephaly, frontonasal encephaloceles and bilateral cleft lip and palate. Malformations also included agenesis of the corpus callosum, abnormal cortical gyres, dilation of the aqueduct, bilateral endolymphatic sac, bilateral cystic cocci-vestibular malformation, and a cribriform defect. The 3D TC craniofacial images showed abnormal frontonasal transition region, with a bone bifurcation, and partial agenesis of nasal bone. The trunk and upper and lower limbs were normal. To our knowledge, this rare association of holoprocensephaly with frontonaso-orbital encephaloceles without limb anomalies has never been reported before. Karyotype was normal. SNP-array showed no copy-number alterations but revealed 25% of regions of homozygosity (ROH) with normal copy number, indicating a high coefficient of inbreeding, which significantly increases the risk for an autosomal recessive disorder. Whole exome sequencing analysis did not reveal any pathogenic or likely pathogenic variants. We discuss the possible influence of two variants of uncertain significance found within the patient's ROHs. First, a missense p.(Gly394Ser) in PCSK9, a gene involved in the regulation of plasma low-density lipoprotein cholesterol. Second, an inframe duplication p.(Ala75_Ala81dup) in SP8, a zinc-finger transcription factor that regulates signaling centers during craniofacial development. Further studies and/or the identification of other patients with a similar phenotype will help elucidate the genetic etiology of this complex case. |
| تدمد: | 1552-4833 1552-4825 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1fec59247c927a459a4bd59a31050433 https://doi.org/10.1002/ajmg.a.61305 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1fec59247c927a459a4bd59a31050433 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15524833 15524825 |
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