Homozygous Autosomal Recessive DIAPH1 Mutation Associated with Central Nervous System Involvement and Aspergillosis: A Rare Case

Abstract

The DIAPH1 gene fulfills critical immune and neurodevelopmental roles. It encodes the mammalian Diaphanous-related formin (mDia1) protein, which acts downstream of Rho GTPases to promote F-actin polymerization and stabilize microtubules. During mitosis, this protein is expressed in human neuronal precursor cells and considerably affects spindle formation and cell division. In humans, dominant gain-of-function DIAPH1 variants cause sensorineural deafness and macrothrombocytopenia (DFNA1), while homozygous DIAPH1 loss leads to seizures, cortical blindness, and microcephaly syndrome (SCBMS). To date, only 16 patients with SCBMS have been reported, none of whom were from Iran. Furthermore, aspergillosis is yet to be reported in patients with homozygous DIAPH1 loss, and the link between SCBMS and immunodeficiency remains elusive. In this study, we shed further light on this matter by reporting the clinical, genetic, and phenotypic characteristics of an Iranian boy with a long history of recurrent infections, diagnosed with SCBMS and immunodeficiency (NM_005219.5 c.3145C > T; p.R1049X variant) following aspergillosis and SARS-CoV-2 coinfection.

An Extended Iranian Family with Autosomal Dominant Non-syndromic Hearing Loss Associated with A Nonsense Mutation in the DIAPH1 Gene

“…8 Until now, there has been no report of DIAPH1 mutations with ADNSHL in any Iranian family. There are only two articles that have been published on the DIAPH1 gene in Iran; one is the introduction of a rare case with homozygous DIAPH1 mutation leading to SCBMS, 9 and the other surveyed the expression patterns of DIAPH1 and virulence genes of dental pathogenic bacteria in oral squamous cell carcinoma patients. 10 Here, we report the first Iranian family with ADNSHL and known nonsense (p.Arg1204Ter) mutation located in the DAD domain near the carboxyl terminus of the DIAPH1 protein.…”