Molecular analysis of holoprosencephaly in South America

Genetics and Molecular Biology

Clarice Pagani Savastano²  Kênia Balbi El-jaick¹  Marcelo Aguiar Costa-lima¹  Cristina Maria Batista Abath¹  Sebastiano Bianca¹  Denise Pontes Cavalcanti¹  Têmis Maria Félix¹  Gioacchino Scarano¹  Juan Clinton Llerena Jr¹  Fernando Regla Vargas¹  Miguel Ângelo Martins Moreira¹  Hector N. Seuánez¹  Eduardo Enrique Castilla²  Iêda Maria Orioli² 

[1] ,Universidade Federal do Rio de Janeiro Departamento de Genética Rio de Janeiro RJ ,Brazil

关键词: holoprosencephaly;    ECLAMC;    SHH;    ZIC2;    SIX3;   

DOI  :  10.1590/S1415-47572014000200011

来源: SciELO

【 摘 要 】

Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.

【 授权许可】

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