NDE1-related disorders: A recurrent NDE1 pathogenic variant causing Lissencephaly 4 can also be associated with microhydranencephaly.

NudE Neurodevelopment Protein 1 (NDE1) gene encodes a protein required for microtubule organization, mitosis, and neuronal migration. Biallelic pathogenic variants of NDE1 gene are associated with structural central nervous system abnormalities, specifically microlissencephaly and microhydranencephaly. The root of these different phenotypes remains unclear. Here, we report a 20-year-old male patient referred to our clinics due to severe microcephaly, developmental delay, spastic quadriplegia, and dysmorphic features. The cranial computed tomography revealed abnormal brain structure and excess of cerebrospinal fluid, consistent with microhydranencephaly. A homozygous c.684_685del, p.(Pro229TrpfsTer85) change in NDE1 gene was found by clinical exome analysis. The variant has previously been reported in individuals with microlissencephaly, therefore we propose that the same variant within the gene may cause either microlissencephaly or microhydranencephaly phenotypes. There are only a few papers about NDE1-related disorders in the literature and the patient we described is important to clarify the phenotypic spectrum of the disease.

A pediatric BAL case with double Ph chromosomes and trisomy 5.

Biphenotypic acute leukemias (BAL) are known as a type of leukemia involving cells with myeloid and along with lymphoid origin, in which genomic changes are detected. It has been stated that the most common genomic changes in BAL are t(9;22) and the translocations of the 11q23 region, these anomalies cause poor prognostic effects. We detected trisomy 5 (+5) in addition to the double Ph chromosome in a case where we investigated the genomic changes using molecular and conventional cytogenetic methods. Bone marrow transplantation was planned due to the poor response to prednisone. According to the information we have obtained, our report will be the first article to discuss the aberrations found in addition to the Ph chromosome in BAL and the effect of these aberrations on prognosis. However, the double observation of the Ph chromosome, which has a poor prognostic effect, is expected to affect the prognosis more negatively, this case will contribute to the literature in terms of trisomy 5. We think that more case reports are needed to reveal the anomalies and their prognostic significance in BAL.

A novel PSEN2 p.Ser175Phe variant in a family with Alzheimer's disease.

Alzheimer's disease (AD) can be either sporadic or familial, and familial forms of AD accounts for only 5% of the cases. So far, autosomal dominantly inherited mutations in "Presenilin 1" (PSEN1), "Presenilin 2" (PSEN2), and "Amyloid precursor protein" (APP) genes were associated with familial AD. Amid the others, pathogenic mutations in the PSEN2 gene are less common. In this study, we describe a novel heterozygous PSEN2 (c.524C>T, p.Ser175Phe) alteration identified in a 58-year-old Turkish patient from a family with multiple dementia cases. This variant was further present in the patient's clinically affected maternal cousin as well as in the asymptomatic mother and two maternal aunts who were carriers of the APOE ε2/ε3 genotype. The variant is located in the conserved residue of transmembrane domain III encoded by exon 6 of the major transcript. In silico protein structure analyses predicted that this variant might change the architecture of interaction between the two alpha helixes of PSEN2. We propose that p.Ser175Phe may have a pathogenic effect on protein function and may play a significant role in the molecular pathways leading to Alzheimer's disease in this family.

A novel SACS p.Pro4154GlnfsTer20 mutation in a family with autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Loss-of-function mutations in the sacsin (SACS) gene lead to autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), impairing the function of sacsin. Genotype-phenotype correlations are still unclear for the different mutations reported in ARSACS. Here, we present a Turkish ARSACS family in whom the novel homozygous frameshift mutation in SACS c.12461delC (p.Pro4154GlnfsTer20) was detected by next-generation sequencing (NGS). The index patient was admitted with progressive spastic ataxia and dysarthria. Since no common mutation in autosomal recessive (AR) cerebellar ataxias, whole gene sequencing provide an advantage to detect novel mutations and may be more effective for clinical diagnosis.