[Genetic diagnosis of microcephaly].

Area of Science:

• Genetics and Genomics
• Developmental Biology
• Medical Diagnostics

Context:

• Microcephaly presents a diagnostic challenge, often requiring advanced genetic testing.
• Traditional karyotype analysis has limitations in detecting smaller chromosomal abnormalities.
• Existing diagnostic methods may not fully elucidate the genetic underpinnings of microcephaly.

Purpose:

• To evaluate the diagnostic efficacy of chromosome karyotype analysis, chromosomal microarray analysis (CMA), and whole exome sequencing (WES) for microcephaly.
• To identify pathogenic genetic variations contributing to microcephaly.
• To analyze gene ontology and gene interaction networks associated with microcephaly-causing genetic alterations.

Summary:

• Nine microcephaly cases were analyzed using karyotype analysis, CMA, and trio-based WES.
• Karyotype analysis yielded no abnormalities. CMA detected one abnormality, while trio-based WES identified likely pathogenic genes in two cases.
• Gene ontology and network analyses provided insights into the functional roles of identified genes and copy number variations (CNVs).

Impact:

• CMA is recommended as a primary diagnostic tool for microcephaly due to its effectiveness.
• Trio-based WES significantly improves the detection rate of pathogenic causes when karyotype and CMA results are negative.
• This study enhances the understanding of genetic mechanisms underlying microcephaly, guiding future diagnostic strategies.