SGSM proteins are small modulator proteins interacting with proteins in the RAS signaling pathway. Studies with mouse and human tissues indicated that SGSM genes were highly expressed in the brain and could be expressed at different levels at different stages of development in fetal and adult brain tissue. It was first reported by Birnbaum et al. that the SGSM3 gene might be associated with a Mendelian inherited disease in families of Ashkenazi Jews with clinical manifestations of intellectual disability (ID). In this study, a novel homozygous stop‐gain (NM_015705.6: c.1576C>T: p.(Arg526Ter)) variation was detected in the SGSM3 gene in two siblings with short stature and ID findings. The report of two cases with bi‐allelic LOF variants in the SGSM3 gene from different populations with similar clinical manifestations strengthens the potential of this gene as a candidate gene for the nonsyndromic ID phenotype. Functional studies are required to investigate the signaling pathways affected by SGSM3 gene variations to produce the ID phenotype and their effect on the functioning of neurons.

Glycogen storage disease type IV (GSD IV) (OMIM #232500) is an autosomal recessive disorder caused by deficiency of the glycogen-branching enzyme. Here, we report a patient presenting with prematurity and severe hypotonia resulting from a complicated pregnancy with polyhydramnios. During her stay in the neonatal unit, the infant remained dependent on a ventilator, and her movements were mostly absent, except for occasional small movements of her fingers. A spontaneous fracture of femur shaft occurred in the postnatal fourth week. Whole-exome sequencing of DNA from the patient revealed a homozygous missense variant in the GBE1 gene (c.1693C>T, p.Arg565Trp). The variation detected in the index case was also confirmed by Sanger sequencing in the patient and respective parents. This study showed that the neuromuscular subtypes of GSD-IV should be considered as a possible differential diagnosis in severe neonatal hypotonia cases.

Deficiency of dedicator of cytokinesis 8 (DOCK8) is a combined immunodeficiency characterized by severe atopic dermatitis, recurrent infections, and elevated serum immunoglobulin E (IgE) levels. Following genetic confirmation, early hematopoietic stem cell transplantation (HSCT) is the treatment of choice. We report a 7-year-old girl who presented with refractory atopic dermatitis and recurrent sinopulmonary infections. Laboratory evaluation revealed markedly elevated total IgE, lymphopenia, decreased memory B cells, and poor vaccine responses. Whole exome sequencing identified a previously unreported homozygous nonsense mutation in the DOCK8 gene (c.5382C>A; p.Tyr1794*). Functional validation was achieved through flow cytometry, which demonstrated significantly reduced DOCK8 protein expression. The patient underwent successful HSCT from a fully matched (10/10) HLA-compatible donor following conditioning with fludarabine and treosulfan. At 1 year follow-up, full donor chimerism was achieved, and the patient remained in remission. This case highlights a novel pathogenic variant in DOCK8 deficiency and demonstrates curative success following definitive diagnosis and timely HSCT.