SASS6 – Primary Autosomal Recessive Microcephaly

Biallelic SASS6 variants have been reported in two probands from unrelated pedigrees: one compound heterozygous splice site mutations c.127-13A>G and c.1867+2T>A in a Chinese family (PMID:30639237) and a homozygous missense mutation in a consanguineous Pakistani kindred (PMID:30639237). SASS6 was also included among 15 MCPH genes identified in consanguineous families with primary microcephaly and intellectual disability (PMID:28674240). These findings support autosomal recessive inheritance with no additional affected relatives reported.

Splice site variants c.127-13A>G and c.1867+2T>A alter mRNA splicing as shown by RT-PCR in patient-derived samples (PMID:30639237), consistent with loss-of-function. SASS6, essential for centriole assembly, likely leads to microcephaly via haploinsufficiency and impaired neurogenesis.

References

• Clinica chimica acta; international journal of clinical chemistry • 2019 • Novel SASS6 compound heterozygous mutations in a Chinese family with primary autosomal recessive microcephaly. PMID:30639237
• Journal of genetics • 2017 • Molecular genetic analysis of consanguineous families with primary microcephaly identified pathogenic variants in the ASPM gene. PMID:28674240

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