-
NeoReviews May 2024
Topics: Humans; Congenital Hypothyroidism; Infant, Newborn; Thyroxine; Follow-Up Studies; Female
PubMed: 38688883
DOI: 10.1542/neo.25-5-e312 -
Environment International May 2024Deep-sea habitats are currently recognized as a hot spot for mercury (Hg) accumulation from anthropogenic sources, resulting in elevated concentrations of total mercury...
Deep-sea habitats are currently recognized as a hot spot for mercury (Hg) accumulation from anthropogenic sources, resulting in elevated concentrations of total mercury (THg) in deep-sea megafauna. Among them, deep-sea sharks (Class Chondrichthyes) are characterized by high trophic position and extended longevity and are, therefore, at high risk for mercury contamination. Despite this, sharks are overexploited by fishing activity in increasingly deeper water, worldwide, imposing health risks to human consumption. While it is imperative to better understand long-term mercury contamination in deep-sea megafauna, few historical data sets exist to capture this process. Here we explore four decades (1985-2022) of THg accumulation in five species of deep-sea sharks (G. melastomus, E. spinax, S. rostratus, C. granulosus, and D. licha) of the ultra-oligotrophic Southeastern Mediterranean Sea (SEMS) sampled during 19 research cruises. We exhibited exceptionally high THg levels (per length/weight), the highest as 16.6 μg g (wet wt.), almost entirely (98.9 %; n = 298 specimens) exceeding the limit for safe consumption (0.3-0.5 μg THg g wet wt.). The maximal THg levels of the long-lived species D. licha and C. granulosus in the SEMS were enriched by a factor of ∼ 7 and >10 compared to counterpart species from other oceanic areas, respectively. We attribute this to the ultra-oligotrophic conditions of the SEMS, which cause slower growth rates and dwarfism in deep-sea sharks, resulting in an extended exposure time to mercury contamination. In the long-lived species, C. granulosus and D. licha, a temporal increase of average THg levels of ∼ 80 % was recorded between 1987-1999 and 2021-2022. This likely reflects the long-term accumulation of historical anthropogenic Hg in deep-sea environments, which is further amplified in marginal seas such as the Mediterranean, impacted by global air pollution crossroads and surrounded by land-based pollution sources. Future consumption of products from deep-sea sharks is potentially high risk to human health.
Topics: Animals; Mercury; Mediterranean Sea; Sharks; Water Pollutants, Chemical; Environmental Monitoring
PubMed: 38688233
DOI: 10.1016/j.envint.2024.108661 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... May 2024To analyze the clinical phenotype and genetic characteristics of a patient with Isidor-Toutain spinal epiphyseal dysplasia (SEMD) due to variant of RPL13 gene.
OBJECTIVE
To analyze the clinical phenotype and genetic characteristics of a patient with Isidor-Toutain spinal epiphyseal dysplasia (SEMD) due to variant of RPL13 gene.
METHODS
A pregnant woman at 18 weeks of gestation who had presented at Quzhou Maternal and Child Health Care Hospital on January 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the patient, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.
RESULTS
The woman was 37 years old with extremely short stature (135 cm) and "O" shaped legs. WES revealed that she has harbored a c.548G>C (p.Arg183Pro) missense variant of the RPL13 gene (NM_000977.4). The same variant was not found in her fetus. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4).
CONCLUSION
Isidor-Toutain type SEMD due to variants of the RPL13 gene may have variable expressivity and diverse clinical phenotypes. Above finding has facilitated the differential diagnosis and genetic counseling for this family.
Topics: Humans; Female; Adult; Ribosomal Proteins; Pregnancy; Exome Sequencing; Phenotype; Osteochondrodysplasias; Dwarfism; Mutation, Missense; Genetic Testing
PubMed: 38684306
DOI: 10.3760/cma.j.cn511374-20220329-00173 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... May 2024To explore the clinical features and genetic etiology of a child with SPONASTRIME dysplasia (SD).
OBJECTIVE
To explore the clinical features and genetic etiology of a child with SPONASTRIME dysplasia (SD).
METHODS
A 9-month-old female who had presented at the Linyi People's Hospital in August 2022 for short stature was selected as the study subject. Clinical data of the child were collected, and whole exome sequencing (WES) was carried out. Sanger sequencing was used for validating the candidate variants.
RESULTS
The child has manifested short stature, mid-face hypoplasia, joint laxity, internal knee rotation, irregularities in the metaphysis of long bones, and flat and concave lumbar vertebrae. WES revealed that she has harbored compound heterozygous variants of the TONSL gene, namely c.3088G>T (p.Glu1030*) and c.3053G>A (p.Arg1018His), which were inherited from her phenotypically normal parents. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.3088G>T variant was classified as likely pathogenic (PVS1+PM2_Supporting), whilst the c.3053G>A was classified as a variant of uncertain significance (PM2_Supporting+PM3+PP3).
CONCLUSION
The c.3088G>T and c.3053G>A compound heterozygous variants of the TONSL gene probably underlay the pathogenesis in this patient. Above finding has facilitated the clinical diagnosis and genetic counseling for her family.
Topics: Humans; Female; Heterozygote; Infant; Exome Sequencing; Mutation; Dwarfism; Phenotype; Matrilin Proteins
PubMed: 38684304
DOI: 10.3760/cma.j.cn511374-20230426-00244 -
European Journal of Medical Genetics Jun 2024Kenny-Caffey Syndrome (KCS) is a genetic syndrome characterized by growth retardation with short stature, cortical thickening and medullary stenosis of long bones, and...
Kenny-Caffey Syndrome (KCS) is a genetic syndrome characterized by growth retardation with short stature, cortical thickening and medullary stenosis of long bones, and hypoparathyroidism with hypocalcemia. KCS and the related but more severe condition osteocraniostenosis are determined by monoallelic variants in the FAM111A gene. Here we describe the KCS phenotype resulting from the monoallelic FAM111A variant p.Y511H in a 31-year-old woman and in her 56-year-old mother, who is one of the oldest affected individuals known so far. To our knowledge, it is also one of the few molecularly confirmed cases of a mother-to-child transmission of KCS.
Topics: Humans; Female; Phenotype; Adult; Middle Aged; Hyperostosis, Cortical, Congenital; Mothers; Dwarfism; Hypocalcemia; Receptors, Virus
PubMed: 38679371
DOI: 10.1016/j.ejmg.2024.104943 -
Genes Apr 2024(1) Background: Cockayne syndrome (CS) is an ultra-rare multisystem disorder, classically subdivided into three forms and characterized by a clinical spectrum without a...
(1) Background: Cockayne syndrome (CS) is an ultra-rare multisystem disorder, classically subdivided into three forms and characterized by a clinical spectrum without a clear genotype-phenotype correlation for both the two causative genes (CS type B) and (CS type A). We assessed this, presenting a series of patients with genetically confirmed CSB. (2) Materials and Methods: We retrospectively collected demographic, clinical, genetic, neuroimaging, and serum neurofilament light-chain (sNFL) data about CSB patients; diagnostic and severity scores were also determined. (3) Results: Data of eight CSB patients are presented. Four patients had CS I, three patients CS II, and one patient CS III. Various degrees of ataxia and spasticity were cardinal neurologic features, with variably combined systemic characteristics. Mean age at diagnosis was lower in the type II form, in which classic CS signs were more evident. Interestingly, sNFL determination appeared to reflect clinical classification. Two novel premature stop codon and one novel missense variants were identified. All CS I subjects harbored the p.Arg735Ter variant; the milder CS III subject carried the p.Leu764Ser missense change. (4) Conclusion: Our work confirms clinical variability also in the /CSB type, where manifestations may range from severe involvement with prenatal or neonatal onset to normal psychomotor development followed by progressive ataxia. We propose, for the first time in CS, sNFL as a useful peripheral biomarker, with increased levels compared to currently available reference values and with the potential ability to reflect disease severity.
Topics: Humans; Cockayne Syndrome; Poly-ADP-Ribose Binding Proteins; DNA Repair Enzymes; Female; Male; DNA Helicases; Child; Child, Preschool; Adolescent; Retrospective Studies; Adult; Infant; Genetic Association Studies; Young Adult; Transcription Factors
PubMed: 38674442
DOI: 10.3390/genes15040508 -
Nature Apr 2024
PubMed: 38671278
DOI: 10.1038/d41586-024-01201-6 -
Journal of Pediatric Endocrinology &... Jun 2024Transient hyperthyrotropinemia/transient hypothyroxinaemia and congenital hypothyroidism (CH) have completely different treatment and clinical outcomes. However, a...
A novel useful marker in the early discrimination of transient hyperthyrotropinemia/hypothyroxinemia and congenital hypothyroidism in preterm infants: thyroid-stimulating hormone/free thyroxine ratio.
OBJECTIVES
Transient hyperthyrotropinemia/transient hypothyroxinaemia and congenital hypothyroidism (CH) have completely different treatment and clinical outcomes. However, a powerful, highly sensitive and cost-effective marker for the differentiation of these clinical entities in the early postnatal period is not available. Therefore, we aimed to test the potential, early predictive, diagnostic power of the thyroid-stimulating hormone (TSH)/free thyroxine (fT4) ratio for differentiation of the two clinical entities in the early period of life.
METHODS
TSH and fT4 levels were recorded on the postnatal day 7 of premature infants<32 weeks of gestational age. TSH/fT4 ratio was calculated. The significance degree of TSH/fT4 ratio was analyzed for the differentiation of transient hyperthyrotropinemia or transient hypothyroxinaemia and CH.
RESULTS
The study included 1,204 preterm infants<32 weeks of gestational age. Of the 1,204 infants, 978 (81.2 %) had normal thyroid function. Eighty-eight infants (7.3 %) were diagnosed with CH and 138 (11.5 %) with transient hyperthyrotropinemia or transient hypothyroxinemia. Initial TSH/fT4 ratio>4.8 was found to be an early diagnostic warning sign with high power in favor of transient hyperthyrotropinemia or transient hypothyroxinemia (AUC value: 0.947) and TSH/fT4 ratio>12.5 (AUC value: 0.999) was found to be an early diagnostic warning sign with high power in favor of CH (p=0.0001).
CONCLUSIONS
We found for the first time that the TSH/fT4 ratio can be used for the early differentiation of transient hyperthyrotropinemia/transient hypothyroxinaemia and CH in preterm infants without additional cost and with high power.
Topics: Humans; Infant, Newborn; Congenital Hypothyroidism; Thyroxine; Infant, Premature; Thyrotropin; Male; Female; Biomarkers; Hyperthyroxinemia; Gestational Age; Thyroid Function Tests; Prognosis; Diagnosis, Differential; Follow-Up Studies; Infant, Premature, Diseases
PubMed: 38662611
DOI: 10.1515/jpem-2024-0118 -
Scientific Reports Apr 2024The thermal spring-fed Lake Pețea located in NW Romania southeast of the city of Oradea harbors a unique endemic warm water biota. It is the only location in Europe...
The thermal spring-fed Lake Pețea located in NW Romania southeast of the city of Oradea harbors a unique endemic warm water biota. It is the only location in Europe where thermal water endemic melanopsid Microcolpia parreyssii (Philippi, 1847) lived along with the highly endangered warm-water relict neritid Theodoxus prevostianus. Lake Petea's evolution was mainly controlled by major climate-driven hydrological changes also seen in regional records. The hydrological changes were mainly controlled by varying input of thermal water due to recurring increased/decreased recharge of the underground karst water system. The driving factor was warming connected to the interstadial GI 1 increasing recharge by melting of regional ice sheets in the Late Glacial. Conversely, during the Younger Dryas (H0) and the Holocene increasing/decreasing moisture availability was in control. Low stands created multiple bottlenecks reducing genetic variability seen in the appearance of extreme morphologies during next rapid climate melioration. The studied gastropods responded mostly similarly to changes controlling the availability of elements in shell construction and habitat reduction leading to changes in shape, density, size. Periods of lower lake levels and reduced warm water input are characterized by the emergence of elongated tightly coiled shells while globular, compressed loosely coiled shells develop at times of warmer water provision and increased Mg availability. In size there is a contrasting trend. Namely globose Th. prevostianus shells are larger than the elongated ones. Conversely globose, compressed Microcolpia are generally smaller than their elongated spindle-shaped counterparts. In this sense the development of dwarf morphotypes in warmer water habitats is characteristic of Lake Pețea melanopsids. This type of dwarfism i.e. the reduction of shell size is lacking though in Lake Pețea neritids. Our findings also confirm the presence of various ecophenotypes of Microcolpia in the pond degrading our endemic species Mi. parreyssii to a variety of Mi. daudebartii.
PubMed: 38658697
DOI: 10.1038/s41598-024-60185-5 -
Mammalian Genome : Official Journal of... Jun 2024The petit (pet) locus is associated with dwarfism, testicular anomalies, severe thymic hypoplasia, and high postnatal lethality, which are inherited in autosomal...
The petit (pet) locus is associated with dwarfism, testicular anomalies, severe thymic hypoplasia, and high postnatal lethality, which are inherited in autosomal recessive mode of inheritance in rats with a Wistar strain genetic background. Linkage analysis localized the pet locus between 98.7 Mb and 101.2 Mb on rat chromosome 9. Nucleotide sequence analysis identified 2 bp deletion in exon 2 of the Thap4 gene as the causative mutation for pet. This deletion causes a frameshift and premature termination codon, resulting in a truncated THAP4 protein lacking approximately two-thirds of the C-terminal side. Thap4 is expressed in various organs, including the testis and thymus in rats. To elucidate the biological function of THAP4 in other species, we generated Thap4 knockout mice lacking exon 2 of the Thap4 gene through genome editing. Thap4 knockout mice also exhibited dwarfism and small testis but did not show high postnatal lethality. Thymus weights of adult Thap4 knockout male mice were significantly higher compared to wild-type male mice. Although Thap4 knockout male mice were fertile, their testis contained seminiferous tubules with spermatogenesis and degenerative seminiferous tubules lacking germ cells. Additionally, we observed vacuoles in seminiferous tubules, and clusters of cells in the lumen in seminiferous tubules in Thap4 knockout male mice. These results demonstrate that spontaneous mutation of Thap4 gene in rats and knockout of Thap4 gene in mice both cause dwarfism and testicular anomalies. Thap4 gene in rats and mice is essential for normal testicular development, maintaining spermatogenesis throughout the entire region of seminiferous tubules.
Topics: Animals; Male; Dwarfism; Testis; Mice, Knockout; Mice; Rats; Mutation; Rats, Wistar
PubMed: 38658415
DOI: 10.1007/s00335-024-10041-8