Preimplantation genetic testing for monogenic/single gene disorders in a family with Molybdenum co-factor deficiency / 中华医学遗传学杂志

OBJECTIVE@#To carry out preimplantation genetic testing for monogenic/single gene disorders (PGT-M) for a Chinese family affected with Molybdenum co-factor deficiency due to pathogenic variant of MOCS2 gene.@*METHODS@#A family with molybdenum co-factor deficiency who attended to the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region in April 2020 was selected as the research subject. Trophoblast cells were biopsied from blastocysts fertilized by intracytoplasmic sperm injection. Embryos carrying the MOCS2 gene variant and chromosome copy number variation (CNV) of more than 4 Mb were detected by single-cell whole genome amplification, high-throughput sequencing and single nucleotide polymorphism typing. Embryos without or carrying the heterozygous variant and without abnormal chromosome CNV were transplanted. During mid-pregnancy, amniotic fluid sample was collected for prenatal diagnosis to verify the results of PGT-M.@*RESULTS@#Eleven oocytes were obtained, among which three blastocysts were formed through culturing. Results of genetic testing suggested that one embryo was heterozygous for the maternally derived MOCS2 gene variant and without chromosomal CNV. Following embryo transfer, intrauterine singleton pregnancy was attained. Prenatal diagnosis by amniocentesis at 18 weeks of gestation revealed that the MOCS2 gene variant and chromosomal analysis results were both consistent with that of PGT-M, and a healthy male infant was born at 37+5 weeks of gestation.@*CONCLUSION@#PGT-M has helped the couple carrying the MOCS2 gene variant to have a healthy offspring, and may become an important method for couples carrying other pathogenic genetic variants.

Molybdenum cofactor deficiency caused by / 中国当代儿科杂志

A boy attended the hospital at the age of 1 month due to left hand tremor for 1 week. A blood test showed a reduction in serum uric acid and a cranial MRI showed encephalomalacia, atrophy, and cystic changes. The boy had microcephalus, unusual facial features (long face, long forehead, protruded forehead, long philtrum, low nasal bridge, facial swelling, and thick lower lip), hypertonia of lower extremities, and severe global developmental delay. Whole-exome sequencing performed for the boy detected a homozygous mutation, c.217C > T(p.R73W), in the

Extensive pyoderma gangrenosum-like lesions revealing a case of hyperzincemia and hypercalprotectinemia: when to suspect it?

Abstract Hyperzincemia and hypercalprotectinemia is a rare inflammatory disease caused by a mutation in the PSTPIP1 gene, with a dysregulation of calprotectin metabolism. Calprotectin is a zinc-binding protein with antimicrobial properties and pro-inflammatory action. The authors report the case of a 20 year-old girl with cutaneous ulcers comparable with pyoderma gangrenosum, growth failure and chronic anemia, who was given the diagnosis of hyperzincemia and hypercalprotectinemia. Measurement of serum zinc and calprotectin concentrations are indicated in these cases.

The influence of zinc deficiency on chronic pain in Sprague Dawley rats.

Aim Zinc (Zn) defi ciency remains a problem in most developing countries, including Indonesia, especially in the East Nusa Tenggara (NTT) Islands. Zinc plays a major role in pain through the modulation process by the N-methyl-Daspartate (NMDA) receptors, which also includes neuronal nitric oxide synthase (nNOS) as a pain parameter. The purpose of this study is to reveal the effects of Zn towards pain response and modulation stage at the spinal cord level in rats. Methods Twenty Sprague Dawley (SD) rats were divided into two groups, a defi cient group and a normal group. The defi cient group was fed on an IRI-OB diet. Every group was further divided into two more groups, the acute pain group (transient noxious stimuli), and the chronic pain group (continuous noxious stimuli). The rats in chronic pain group were subjected to CCI Bennet operation. The pain thresholds in the defi cient group and normal group were measured clinically using a modifi ed Ugo Basille plantar test (thermal transient noxious stimuli). Measurement of chronic pain level was carried out by measuring the nNOS level by immunohistochemistry. Results Defi cient group showed an insignifi cant decrease in pain threshold (P= 0.251). However, there is a signifi cant increase in nNOS (P= 0.027) especially in the defi cient group with continuous noxious stimulation. Conclusions These results suggest that Zn defi ciency increases pain response, especially in chronic pain.

Inherited canine copper toxicosis in Australian Bedlington Terriers

Inherited copper toxicosis in Bedlington Terriers (CTBT) is a copper associated hepatopathy caused by an autosomal recessive genetic defect of gene involving copper metabolism. To compare clinical and histopathological findings with previous reports and to expand our knowledge for future genetic studies, 18 terriers were clinically and histopathologically examined in this study. Pedigree information and dietary history were obtained from the owners before a thorough clinical examination was undertaken. Following the examination, a blood sample was collected for haematology, biochemistry and genetic analysis and a urine sample for urinalysis. Seven dogs were also liver biopsied for histopathology, histochemistry and electron microscopy. In this study, plasma alanine transaminase (ALT) activity was highly concordant with DNA marker test results and was the most reliable and sensitive biochemical test measured. Also clinical and biochemical copper toxicosisaffected states were noticed in a genotyped carrier dog. Histopathological and electron microscopy findings showed that the severity of the lesion was more closely correlated to the presence of clinical signs than to hepatic copper concentration. In addition, the involvement of apoptosis and p53 gene was observed in electron microscopy. The general findings related to CT-BT in this study was similar to those previously reported except few differences in histopathology and electron microscopy.

Diagnostic potential of histochemical demonstration for copper-orcein stain.

The histochemical demonstration of hepatic copper is important in the diagnosis of paediatric copper storage disorders. Conflicting results have been published regarding ability of different histochemical stains to demonstrate copper storage in the liver. Hence the authors retrospectively analysed eighty-two liver biopsies from 82 patients of Indian childhood cirrhosis (ICC), 59 males and 23 females aged between 1-4 years (mean age 3.1 years). All cases were stained with orcein stain. On the basis of histological picture the liver biopsies were divided into the three histological grades I, II and III. Orcein positively was graded from I to IV. All cases showed positivity with orcein stain. Most cases showed grades II and III of orcein positivity. The association between histological and orcein grades was significant. The present study demonstrates the diagnostic utility of orcein stain in liver copper storage disorder, Indian childhood cirrhosis. Variable copper content in the same histological grade of the disease could be due to individual factors such as genetic milieu which determine the amount of copper liver can store without toxicity.

Erros inatos do metabolismo e epilepsia / Inborn errors of metabolism and epilpsy

O autor revisa aqui erros inatos do metabolismo (EIM) que podem ter crises convulsivas entre suas manifestaçöes clínicas. Os mecanismos epileptogênicos distintos de cada EIM säo abordados ou ao menos sugeridos e, a seguir dá-se um roteiro de abordagem diagnóstica das convulsöes, com possível etiologia metabólica

El cobre como mineral esencial para la nutricion humana. / Copper as an essential mineral for human nutrition

Se revisa el rol del cobre como elemento esencial para la nutricion humana. El cobre es necesario para el hombre por su participacion como componente de importantes sistemas enzimaticos. Los mas conocidos son el de la ceruloplasmina, superoxidismutasa, lisil oxidasa y citrocromo c oxidasa. En condiciones habituales de alimentacion el aporte nutricional de cobre es suficiente, ya que casi todos los alimentos lo contienen. En los ultimos anos se han descrito deficiencias de cobre en lactantes que han recibido por largo tiempo dietas basadas exclusivamente en leche de vaca.La alimentacion parenteral prolongada y la malabsorcion intestinal son otros factores que pueden provocarla. Las manifestaciones clinicas de la deficiencia de cobre incluyen neutropenia, leucopenia, anemia hipocroma resistente a la terapia con hierro y alteraciones oseas semejantes al raquitismo. Las recomendaciones de aporte para lactantes son de 80 micrograma por kg por dia de cobre. Se recomienda la suplementacion con cobre de los alimentos destinados a los lactantes que presenten condiciones que favorezcan la deficiencia