Background Variants in the DEPDC5 have been proved to be main cause of not only various dominant familial focal epilepsies, but also sporadic focal epilepsies. In the present study, a novel variant in DEPDC5 was detected in the patient with focal epilepsy and his healthy father. We aimed to analyze the pathogenic DEPDC5 variant in the small family of three. Case presentation A 5-month-old male infant presented with focal epilepsy. Whole exome sequencing identified a novel heterozygous variant c.1696delC (p.Gln566fs) in DEPDC5, confirmed by Sanger sequencing. The variant was inherited from healthy father. Conclusions Our study expands the spectrum of DEPDC5 variants. Moreover, We discuss the relation between the low penetrance of DEPDC5 and the relatively high morbidity rate of DEPDC5-related sporadic focal epilepsy. Besides, due to interfamilial phenotypic and genetic heterogeneity, we speculate the prevalence of familial focal epilepsy with variable foci might be underestimated in such small families. We emphasize the importance of gene detection in patients with sporadic epilepsy of unknown etiology, as well as their family members. It can identify causative mutations, thus providing help to clinicians in making a definitive diagnosis.
Background: PIGA (PIG class A) gene codes the PIG-A protein, which is a catalytic subunit of GPI-GlcNAc transferase. GPI-anchored proteins play important roles in the metabolism of mammals. Somatic variants of PIGA genes of bone marrow hematopoietic stem cells often result in Paroxysmal Nocturnal Haemoglobinuria, and the germline PIGA variant causes multiple congenital anomalies hypotonia seizures syndrome 2 (MCAHS2) because of glycosylphosphatidylinositol metabolic abnormalities. Methods: Whole exome sequencing was performed on peripheral blood samples of the proband with MCAHS2. A novel germline PIGA variant were found, and Sanger sequencing was performed as veri cation for the variants. Then we used the keywords to retrieve relevant reports and provided a literature review.Results: A novel hemizygous germline PIGA variant (NM_002641.3:c.971G>A) at exon4 was identi ed through the outcomes of whole exome sequencing. And it is highly probable pathogenic variant. Sanger sequencing yielded consistent results. The missense variant cause change of p.(Cys324Tyr) in the transcription product according to the predicting outcomes. Conclusion:We reported a case of MCAHS2 caused by navel PIGA variant. Following a review of the literature, we suggest that MCAHS2 should be considered as a disorder spectrum consisting of core symptoms, multi-system impairment, and premature death. The core symptoms include of hypotonia, psychomotor delay, epilepsy (intractable epilepsy mostly) and early death. Core symptoms nearly happened to almost all patients. Meanwhile MCAHS2 involves a wide range of organ and system impairments with changeable form. Introduction:Glycosylphosphatidylinositol (GPI) is a lipid anchor by which at least 150 proteins are attached to the cell membrane. Those proteins are termed as GPIanchored proteins (GPI-APs) [1, 2]. The special carboxyl terminus of GPI has a hydrophobic terminal as signal sequence [3,4]. GPI precursors are synthesized through a series of enzymatic reactions in the endoplasmic reticulum. By a transamidation reaction, GPI-transamidases recognize the signal sequence of the proteins and replace it with GPI precursors [4,5]. GPI-APs play an important role in the metabolism of mammals, involving many functional proteins such as hydrolytic enzymes, adhesion molecules, receptors, protease inhibitors and complement regulatory proteins[1, 2, 5]. These GPI-APs are particularly essential for the embryogenesis, neurogenesis, fertilization and immune system[6]. At least 26 genes have been found tightly related to GPI biosynthesis, the processes of GPI binding to proteins and remodeling of side branches [1]. These genes were named as PIG (for Phosphatidyl Inositol Glycan), and at least three genes including of class A, C and H (usually called PIGA, PIGC and PIGH) are involved in the rst step of GPI biosynthesis. PIGA (PIG class A) gene codes the PIG-A protein, which is a catalytic subunit of GPI-GlcNAc transferase located at Xp22.2 [1]. The pathway of GPI synthesis could be divided in several subdivisions:...
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