To the Editor, ZIP7 deficiency is the most recently described congenital agammaglobulinemia with autosomal recessive inheritance. 1 ZIP7, encoded by SLC39A7, is an endoplasmic reticulum-to-cytoplasm Zn 2+ transporter. Developing B cells are sensitive to altered Zn 2+ distribution, which causes developmental blockade beyond the pre-B cell stage. 2 Complete loss of ZIP7 in cell lines causes a reduction in cytoplasmic Zn 2+ and an increase in endoplasmic reticulum Zn 2+ concentration. Since the original report in 2019, no additional cases of ZIP7 deficiency have been published. Here, we describe a patient evaluated for recurrent respiratory tract infections, meningitis, agammaglobulinemia, and B cell lymphopenia, ultimately found to carry a novel SLC39A7 variant. We describe his clinical characteristics, immunological findings, and genetic investigations.We also report on the impact of the J Project (JP) in improving primary immunodeficiency (PID) patient care and research in Eastern and Central Europe (ECE).The patient and his family members were interviewed, examined, treated, and monitored at the University Clinic for Children's Disease in Skopje. Medical records were obtained from the electronic registry of the University Clinic. The mother of the patient has given written informed consent to conduct the study and for the publication of data. All procedures were performed in accordance with the ethical standards of the Institutional Research Committee.Genomic DNA from the patient and his family members was isolated with the Gen Elute Blood Genomic DNA kit (Sigma-Aldrich) and subjected to whole-exome sequencing (WES) in the patient and targeted gene sequencing in the patient and available family members. 3 WES was performed at the New York Genome Center and the Rockefeller University using an Illumina HiSeq 2500 sequencing system (Illumina). Exome capture was carried out with SureSelect human all exome kit (Agilent) in accordance with the manufacturer's instructions. Putative disease alleles found by WES were validated by dideoxy Sanger sequencing in the patient AND in family members. Exons and flanking intronic regions of SLC39A7 wereThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

A novel mutation in SLC39A7 identified in a patient with autosomal recessive agammaglobulinemia To the Editor, ZIP7 deficiency is the most recently described congenital agammaglobulinemia with autosomal recessive inheritance (1). ZIP7, encoded by SLC39A7, is an endoplasmic reticulum-to-cytoplasm Zn 2+ transporter. Developing B cells are sensitive to altered Zn 2+ distribution which cause developmental blockade beyond the pre-B cell stage (2). Complete loss of ZIP7 in cell lines causes a reduction in cytoplasmic Zn 2+ and an increase in endoplasmic reticulum Zn 2+ concentration. Since the original report in 2019, no additional cases of ZIP7 deficiency have been published. Here we describe a patient evaluated for recurrent respiratory tract infections, meningitis, agammaglobulinemia and B cell lymphopenia, ultimately found to carry a novel SLC39A7 variant. We describe his clinical characteristics, immunological findings, and genetic investigations.The patient and his family members were interviewed, examined, treated and monitored at the University Clinic for Children's Disease in Skopje. Medical records were obtained from the electronic registry of the University Clinic. The mother of the patient has given written informed consent to conduct the study and for publication of data. All procedures were performed in accordance with the ethical standards of the Institutional Research Committee. Genomic DNA from the patient and his family members was isolated with the Gen Elute Blood Genomic DNA kit (Sigma-Aldrich) and subjected to whole-exome sequencing (WES) in the patient and targeted gene sequencing in the patient and available family members (3). WES was performed at the New York Genome Center and the Rockefeller University using an Illumina HiSeq 2500 sequencing system (Illumina). Exome capture was carried out with SureSelect human all exome kit (Agilent) in accordance with the manufacturer's instructions. Putative disease alleles found by WES were validated by dideoxy Sanger sequencing in the patient as well as in family members.Exons and flanking intronic regions of SLC39A7 were amplified by PCR. Amplicons were sequenced with the Big Dye Terminator cycle sequencing kit (Applied Biosystems) and targeted regions were analyzed by an ABI 3130 capillary sequencer (Applied Biosystems). Sequence variants were determined by comparing to the appropriate GenBank reference sequence to identify the position of mutations.The patient, a 14-year-old male and the third child in a Macedonian family with Albanian origin was born at term (Fig. 1). Birth weight and length were in the normal ranges and neonatal adaptation was uneventful. Consanguinity in the family was not reported. The patient received only BCG vaccination at birth indicated by a small scar on the left shoulder. He had suffered from recurrent upper and lower respiratory

Tibial aplasia is an uncommon lower limb malformation that can occur isolated or be part of a more complex malformation pattern. We describe a 9-year-old boy born after uneventful pregnancy and delivery. Family history was negative for maternal diabetes and other malformations. The patient presented with left tibial aplasia and homolateral prexial foot polydactyly. He also displayed enamel dysplasia and bifid scotum with cryptorchidism. Literature review failed to identify a significant syndromic association between lower limb defects of the tibial type and the genital anomalies reported here. The combination of tibial aplasia with midline genital malformations further supports the hypothesis that the tibial ray development mirrors the morphogenetic process of the radial structures. Accordingly, the malformation pattern observed in the present patient may be pathogenetically explained by an insult occurring during late blastogenesis.

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