Related Experiment Video
Updated: Jun 30, 2025
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Novel biallelic SASS6 variants associated with primary microcephaly and fetal growth restriction
Xiangtian Kong1, Jian Xu2, Honggang Yin3
1Department of Medical Genetics and Prenatal Diagnosis, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, China.
Abstract:
Primary microcephaly is characterized by a head circumference prenatally or at birth that falls below three standard deviations from age-, ethnic-, and sex-specific norms. Genetic defects are one of the underlying causes of primary microcephaly. Since 2014, five variants of the SASS6 gene have been identified as the cause of MCPH 14 in three reported families. In this study, we present the genetic findings of members of a nonconsanguineous Chinese couple with a history of microcephaly and fetal growth restriction (FGR) during their first pregnancy. Utilizing trio whole-exome sequencing, we identified compound heterozygous variants involving a frameshift NM_194292.3:c.450_453del p.(Lys150AsnfsTer7) variant and a splice region NM_194292.3:c.1674+3A>G variant within the SASS6 gene in the affected fetus. Moreover, reverse transcriptase-polymerase chain reaction from RNA of the mother's peripheral blood leukocytes revealed that the c.1674+3A>G variant led to the skipping of exon 14 and an inframe deletion. To the best of our knowledge, the association between FGR and SASS6-related microcephaly has not been reported, and our findings confirm the pivotal role of SASS6 in microcephaly pathogenesis and reveal an expanded view of the phenotype and mutation spectrum associated with this gene.
Insights
Genetic variants in the SASS6 gene cause primary microcephaly, a condition of small head size. This study identifies new SASS6 variants linked to microcephaly and fetal growth restriction (FGR).
Area of Science:
- Genetics
- Developmental Biology
- Human Pathologies
Background:
- Primary microcephaly is a neurodevelopmental disorder defined by a significantly smaller head circumference than typical.
- Genetic mutations are a known cause of primary microcephaly, with several SASS6 gene variants previously identified.
- The SASS6 gene plays a crucial role in brain development and ciliogenesis.
Observation:
- This study investigated a nonconsanguineous Chinese couple experiencing microcephaly and fetal growth restriction (FGR) in their pregnancy.
- Trio whole-exome sequencing identified compound heterozygous variants in the SASS6 gene of the affected fetus.
- Specific variants found were a frameshift variant (c.450_453del) and a splice region variant (c.1674+3A>G).
Findings:
- The splice region variant (c.1674+3A>G) was shown to cause exon 14 skipping, resulting in an in-frame deletion.
- These SASS6 gene variants are associated with both primary microcephaly and fetal growth restriction (FGR).
- This expands the known phenotypic spectrum and mutation landscape for SASS6-related microcephaly.
Implications:
- The findings underscore the critical role of the SASS6 gene in human brain development.
- This research highlights a previously unreported association between SASS6 mutations and fetal growth restriction.
- Understanding these genetic underpinnings can aid in diagnosing and potentially managing microcephaly and associated growth disorders.
More Related Videos
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017
09:37Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
Related Concept Videos
01:33Pleiotropy
01:07Teratogenicity
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
02:30Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:43Incomplete Dominance
01:35Pedigree Analysis