Two SMARCAD1 Variants Causing Basan Syndrome in a Canadian and a Dutch Family.

Area of Science:

• Genetics
• Dermatology
• Molecular Biology

Background:

• Basan syndrome is a rare autosomal dominant genodermatosis.
• It is characterized by congenital adermatoglyphia, transient congenital facial milia, neonatal acral bullae, and absent or reduced sweating.
• Previously reported variants are primarily point mutations in the SMARCAD1 gene's skin-specific isoform.

Purpose of the Study:

• To identify and characterize novel SMARCAD1 variants in families with Basan syndrome.
• To investigate the genotypic and phenotypic spectrum of Basan syndrome.
• To elucidate the functional consequences of identified SMARCAD1 variants.

Main Methods:

• Whole-genome optical mapping and whole-genome sequencing were used to identify a complex structural variant in one family.
• Whole-exome sequencing was employed to detect a deletion in the second family.
• Phenotypic analysis of affected individuals was conducted.

Main Results:

• Two new SMARCAD1 variants associated with Basan syndrome were identified in two families.
• A complex structural variant (deletion and inverted duplication) affecting SMARCAD1 was found, yet resulted in a typical Basan phenotype.
• A 12-base pair deletion spanning the exon-intron junction of the alternative exon 1 of the skin-specific SMARCAD1 isoform was identified in the second family.

Conclusions:

• Two additional families with Basan syndrome and distinct SMARCAD1 pathogenic variants are reported.
• The findings suggest that a single copy of full-length SMARCAD1 may be sufficient for its function, independent of the skin-specific isoform.
• This study expands the known genetic causes of Basan syndrome and contributes to understanding SMARCAD1 gene function.