A Novel Variant in the DIAPH1 Gene Causing Macrothrombocytopenia and Non-syndromic Hearing Loss in a Pediatric Saudi Girl.

Macrothrompocytopenia (MTP) is a rare group of hereditary disorders that lead to impaired hemostasis. Macrothrompocytopenia mostly results from genetic mutations in genes implicated in megakaryocyte differentiation and function. Diaphanous-related formin 1 (DIAPH1) is a protein-coding gene. Dominant gain-of-function DIAPH1 variants cause macrothrombocytopenia and sensorineural deafness (autosomal dominant non-syndromic hearing loss 1 (DFNA1)), while homozygous loss of DIAPH1 results in seizures, cortical blindness, and microcephaly syndrome (SCBMS). This rare genetic disease is characterized by progressive and severe hearing loss with onset in the first decade of life, is associated with mild thrombocytopenia, and has no significant bleeding tendency. This case report presents the clinical findings of a 14-year-old Saudi pediatric girl. We investigated the potential association of DIAPH1 as a novel candidate gene linked to dominant MTP and autosomal dominant non-syndromic hearing loss (ADNSHL), which was evaluated through audiometry. Notably, a novel variant, c.3633_3636del, was identified in the DIAPH1 gene. To date, only a small number of mutations in this gene have been reported as the cause of MTP and ADNSHL.

A Novel Variant of the LMAN1 Gene in Combined Factor V and Factor VIII Deficiency in a Saudi Female Child: A Case Report.

Combined factor V and factor VIII deficiency (F5F8D) is an exceedingly rare autosomal recessive disease that causes concomitantly low levels of factor V and factor VIII, leading to mild to moderate bleeding tendencies. Within this disorder, mutations manifest in the lectin mannose-binding protein (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) genes. This report presents a case of a five-year-old Saudi female child who was referred from an otolaryngology clinic, with an incidental finding of prolonged prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) detected during routine preoperative investigations for tonsillectomy, prompting further investigations. There was no prior history of bleeding symptoms in the patient. She was discovered to have low assays of factor V and factor VIII on subsequent investigations. Whole exome sequencing revealed the novel homozygous mutation c.604C>T in the LMAN1 gene, validating the diagnosis of F5F8D.