Basan gets a new fingerprint: Mutations in the skin‐specific isoform of SMARCAD1 cause ectodermal dysplasia syndromes with adermatoglyphia

Abstract

Basan syndrome is an autosomal dominant ectodermal dysplasia (ED) with congenital adermatoglyphia, transient neonatal acral bullae, and congenital facial milia. Autosomal dominant adermatoglyphia (ADG) is characterized as adermatoglyphia with hypohidrosis. Recently mutations in the skin‐specific isoform of the gene SMARCAD1 have been found in both syndromes. This report proposes to unify these two previously distinct ED, into one syndrome. We offer a new acronym: SMARCAD syndrome (SMARCAD1‐associated congenital facial Milia, Adermatoglyphia, Reduced sweating, Contractures, Acral Bullae, and Dystrophy of nails). Sanger sequencing was performed on genomic DNA from a patient with Basan syndrome using primers designed to flank SMARCAD1. Sanger sequencing revealed a novel variant, NM_001254949.1:c.‐10 + 2 T > G, in the donor splice site of exon 1 of the skin‐specific isoform. This variant and the other five previously reported variants in Basan syndrome and ADG are all within the same donor splice site. We conclude that Basan syndrome and ADG are on a phenotypic spectrum of a monogenic syndrome which is better described by the acronym SMARCAD syndrome.

The simian crease: Relationship to various genetic disorders

“…The knockdown of SMARCAD‐1 in human keratinocytes resulted in abnormal expression of genes that correspond to epidermal growth factor receptor regulation, keratinocyte proliferation and differentiation, and psoriasis, all of which are relevant to ADG. Valentin et al () proposed unifying Basan syndrome and ADG on the basis of the involvement of SMARCAD‐1 mutation in both syndromes as well as their symptom overlap, called SMARCAD syndrome ( SMARCAD‐1 associated congenital facial Milia, Adermatoglyphia, Reduced sweating, Contractures, Acral bullae, and Dystrophy of nails).…”

“…Regrettably, no evidence in the current literature points specifically to any genetic connection between SMARCAD‐1 and simian creases; at this point, simian creases function as indicators of a much larger congenital defect with no clear genetic or environmental cause. Furthermore, the latest findings regarding SMARCAD‐1 do not suggest that it is responsible for simian creases, but may be linked to adermatoglyphia (Basan syndrome) (Valentin et al, ). Pitt‐Hopkins syndrome (OMIM 610954) (PTHS) is the result of a mutation of the TCF4 gene on Chromosome 18q21, with telling characteristics such as wide mouth and breathing abnormalities (e.g., intermittent overbreathing or sleep apnea).…”

Ectodermal dysplasia with congenital adermatoglyphia (Basan syndrome): Report of two cases presenting with extensive congenital milia

“…Full‐length SMARCAD1 isoform is expressed ubiquitously; the short isoform has a unique 5’‐nontranslated exon (exon 1) and is mainly identifiable in skin fibroblasts. Mutations in the skin‐specific isoform of SMARCAD1 have been confirmed to be the cause of this syndrome in all reported cases 2‐5 . Autosomal dominant adermatoglyphia is also characterized by lack of dermatoglyphics and hypohidrosis.…”

“…Mutations in the skin-specific isoform of SMARCAD1 have been confirmed to be the cause of this syndrome in all reported cases. [2][3][4][5] Autosomal dominant adermatoglyphia is also characterized by lack of dermatoglyphics and hypohidrosis. SMARCAD1 mutations have been found in both syndromes and Valentin et al 4 propose the term SMARCAD syndrome to define a phenotypic spectrum of a monogenic syndrome that includes these entities.In conclusion, we present two cases of Basan syndrome presenting with extensive congenital milia.…”

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

“…It is worth noting that there is no counterpart for the human skinspecific isoform in mouse Smarcad1 (University of California Santa Cruz Genome Browser on Mouse, mm10). Heterozygous variants in the skin-specific isoform are associated with three allelic autosomal dominant syndromes: Basan syndrome, isolated adermatoglyphia (Online Mendelian Inheritance in Man #136000), and Huriez syndrome (Online Mendelian Inheritance in Man #81600) (Burger et al, 2011;Lee et al, 2000;Marks et al, 2014;Nousbeck et al, 2011;Valentin et al, 2018). The three syndromes are characterized by adermatoglyphia and overlap in other clinical features (Günther et al, 2018).…”