Abstract:
BACKGROUND:Fanconi anemia (FA) is phenotypically diverse, hereditary condition associated with bone marrow failure, multiple physical abnormalities, and an increased susceptibility to the development of malignancies. Less recognized manifestations of FA include endocrine abnormalities. International discourse has highlighted that these abnormalities are widespread among children and adults with FA. To date there has been no systematic study that has evaluated the endocrine abnormalities in a cohort of patients with FA, homozygous for a founder mutation (c.637_643del (p.Tyr213Lysfs*6)) in FANCG. The objectives of the study were to evaluate endocrine gland function in patients with FA of a single FA genotype, and to determine the frequency and nature of endocrine abnormalities in this group. METHODS:Cross-sectional, descriptive study of 24 South African patients of African ancestry with FA (homozygous for a FANCG founder mutation). Outcomes measured included growth, pubertal status, growth hormone axis screening, thyroid gland function, glucose and insulin metabolism and bone age (BA). RESULTS:Endocrine dysfunction was present in 70.8% (17 of 24), including abnormal insulin-like growth factor 1 (IGF-1)/insulin-like growth factor-binding protein 3 (IGFBP-3) in 25.0% (6 of 24), insulin resistance in 41.7% (10 of 24), abnormal thyroid function in 16.7% (4 of 24) and short stature in 45.8% (11 of 24). No abnormalities of glucose metabolism were identified. Abnormal pubertal status was seen in three males (12.5%). Abnormal BAs were present in 34.8% (8 of 23). CONCLUSION:Endocrine abnormalities occur at a high frequency in patients with FA, homozygous for a FANCG founder mutation, similar to other FA cohorts. Our data are specific to FA patients with a single genotype, and therefore provide the first genotype-phenotype information on endocrine abnormalities in South African patients, homozygous for a FANCG founder mutation. Recommendations regarding endocrine screening in this patient subgroup are made, including, but not limited to, baseline testing of thyroid function, fasted insulin and glucose, and IGF-1 and IGFBP-3.
journal_name
Mol Genet Genomic Medjournal_title
Molecular genetics & genomic medicineauthors
Dillon B,Feben C,Segal D,du Plessis J,Reynders D,Wainwright R,Poole J,Krause Adoi
10.1002/mgg3.1351subject
Has Abstractpub_date
2020-08-01 00:00:00pages
e1351issue
8issn
2324-9269journal_volume
8pub_type
杂志文章abstract:BACKGROUND:Due to extensive clinical and genetic heterogeneity of intellectual disability (ID) syndromes, the process of diagnosis is very challenging even for expert clinicians. Despite recent advancements in molecular diagnostics methodologies, a significant fraction of ID patients remains without a clinical diagnosi...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1263
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Apolipoprotein E (ApoE) is a glycoprotein that plays an important role in lipid homeostasis at both cerebral and systemic levels. Moreover, the differential distribution of APOE gene alleles among different populations, means that ApoE isoforms could have different effects on lipids metabolism. The present s...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.958
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:Maple sirup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder. The disease-causing mutations can affect the BCKDHA, BCKDHB, and DBT genes encoding for the E1α, E1β, and E2 subunits of the multienzyme branched-chain α-keto acid dehydrogenase (BCKDH) complex. In the present study, nov...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1337
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Aneurysmal subarachnoid hemorrhage (aSAH) has high fatality and permanent disability rates due to the severe damage to brain cells and inflammation. The SERPINE1 gene that encodes PAI-1 for the regulation of tissue plasminogen activator is considered an important therapeutic target for aSAH. METHODS:Six SNP...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.737
更新日期:2019-08-01 00:00:00
abstract::The impact of cryptic relatedness (CR) on genomic association studies is well studied and known to inflate false-positive rates as reported by several groups. In contrast, conventional epidemiological studies for environmental risks, the confounding effect of CR is still uninvestigated. In this study, we investigated ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.4
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:Male-specifically inherited Y-STRs have been widely used in population genetics and forensic investigations. METHODS:We genotyped and analyzed Y chromosome haplotypes of 408 unrelated Tibeto-Burman-speaking Yi male individuals from Guizhou using Goldeneye® Y-PLUS kit. Population comparisons between the Guiz...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1572
更新日期:2021-01-15 00:00:00
abstract:BACKGROUND:Malan syndrome is a recently introduced overgrowth disorder described in a limited number of individuals. Haploinsufficiency and also point mutations of NFIX gene have been proposed as its leading causative mechanism, however, due to the limited number of cases and different deletion sizes, genotype/phenotyp...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章,评审
doi:10.1002/mgg3.997
更新日期:2019-12-01 00:00:00
abstract::Considering that variability in immune response genes has been associated with susceptibility to leprosy and with disease severity, leprosy presents clinicopathological variants that are highly associated with the immune response, HLA-G has a well-recognized role in the modulation of the immune response, and polymorph...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.14
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:There have been many reports on midkine as a promising marker in the diagnosis of hepatocellular carcinoma (HCC). However, the results are inconsistent and even conflicting. METHODS:This meta-analysis was performed to investigate the accuracy of midkine in the diagnosis of HCC. Meta-DiSc 1.4 software was us...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章,评审
doi:10.1002/mgg3.1071
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.291
更新日期:2017-04-23 00:00:00
abstract:BACKGROUND:Tuberculosis (TB) is a significant worldwide health problem, and is caused by Mycobacteria tuberculosis. Recent studies have suggested that FOXO3 plays vital roles in the risk of immune-related infectious diseases such as TB. METHODS AND RESULTS:The present study aimed to evaluate FOXO3 genetic variants and...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.770
更新日期:2019-08-01 00:00:00
abstract::Definitive diagnosis of primary hyperoxaluria (PH) currently utilizes sequential Sanger sequencing of the AGXT, GRPHR, and HOGA1 genes but efficacy is unproven. This analysis is time-consuming, relatively expensive, and delays in diagnosis and inappropriate treatment can occur if not pursued early in the diagnostic wo...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.118
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Congenital scoliosis (CS) is defined as a lateral curvature of the spine due to the vertebral malformations and has an incidence of 0.5-1/1,000 births. We previously examined TBX6 in Japanese CS patients and revealed that approximately 10% of CS was caused by TBX6 mutations. However, the genetic cause of rem...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.466
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Retinoblastoma (Rb) is a rare intraocular malignant tumor in children with high overall survival. Predisposition to Rb is linked to RB1 germline mutations with high penetrance, but rare RB1 low-penetrance variants are also known. Rb survivors are at risk of second primary malignancies (SPMs), mostly osteosar...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.913
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:TOP2B encodes type II topoisomerase beta, which controls topological changes during DNA transcription. TOP2B is expressed in the developing nervous system and is involved in brain development and neural differentiation. Recently, a de novo missense TOP2B variant (c.187C>T) has been identified in an individua...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1145
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45 cases from 27 families have been reported, and the pathogenic bi-allelic mutations in FLVCR2 gene described in 15 families. The pathogenesis of...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.376
更新日期:2018-05-01 00:00:00
abstract:BACKGROUND:The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervo...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1559
更新日期:2021-01-19 00:00:00
abstract:PURPOSE:To assess clinical chromosomal microarray (CMA) genomic testing reports for the following: (a) usage of reporting elements consistent with 2011 ACMG guidelines and other elements identified in the primary literature, (b) information quality, and (c) readability. METHODS:We retrospectively analyzed genomic test...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.551
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI incl...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1076
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:MicroRNA-33a (miR-33a) plays the role of the tumor suppressor gene by regulating the expression level of downstream genes. However, the effects of miR-33a in renal cell cancer (RCC) remain unknown. Our study was designed to investigate the expression level and potential function of miR-33a in RCC. METHODS:R...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.833
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:The protein NgR1 is encoded by RTN4R, a gene linked to schizophrenia. We previously reported NgR1 as receptor for the epilepsy-linked protein LGI1. NgR1 regulates synapse number and synaptic plasticity, whereas LGI1 antagonizes NgR1 signaling and promotes synapse formation. Impairments in synapse formation a...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.215
更新日期:2016-03-11 00:00:00
abstract:BACKGROUND:The Latrophilin 3 (LPHN3) gene (recently renamed Adhesion G protein-coupled receptor L3 (ADGRL3)) has been linked to susceptibility to attention deficit/hyperactivity disorder (ADHD) and vulnerability to addiction. However, its role and function are not well understood as there are no known functional varian...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.207
更新日期:2016-03-04 00:00:00
abstract:OBJECTIVES:This study aimed to investigate and confirm the association between 15 single nucleotide polymorphisms of four susceptibility genes (NBS1, TP53, PTEN, and BRIP1) and the susceptibility of breast cancer. METHODS:The genome DNA was extracted from peripheral blood and tumor tissues from one hundred and sevente...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1578
更新日期:2021-01-05 00:00:00
abstract:BACKGROUND:Milroy-like disease is the diagnostic definition used for patients with phenotypes that resemble classic Milroy disease (MD) but are negative to genetic testing for FLT4. In this study, we aimed at performing a genetic characterization and biochemical analysis of VEGF-C variations found in a female proband b...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1389
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:This study investigated the effects of haplotypes T-G and C-A derived from NG_012836.1:g.4160T>C and NG_012836.1:g.4326G>A on protein expression levels in vitro and identified the functional sequence in the regulatory region of the GABRB3 gene linked to possible associations with schizophrenia. METHODS:Reco...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.652
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Johanson-Blizzard syndrome (JBS, MIM #243800) is a very rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, nasal wing hypoplasia, hypodontia, and other abnormalities. JBS is caused by mutations of the UBR1 gene (MIM *605981), encoding a ubiquitin ligase of the N-end rule pa...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.319
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:22q11 deletion syndrome (22qDS) is caused by deletion of chromosome region 22q11.2. However, mosaic cases with 22q11.2 deletion syndrome (22q11.2DS) are rarely reported. METHODS:Chromosomal microarray analysis (CMA) and fluorescence in situ hybridization fluorescence in situ hybridization (FISH) were perfor...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.847
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Medulloblastomas (MBs) are a heterogeneous group of childhood brain tumors with four consensus subgroups, namely MBSHH , MBWNT , MBGroup 3 , and MBGroup 4 , representing the second most common type of pediatric brain cancer after high-grade gliomas. They suffer from a high prevalence of genetic predispositio...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1302
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Recently hyperphenylalaninemia (HPA) caused by variants in DNAJC12 was reported and this suggested a new strategy for diagnosis. But DNAJC12-associated HPA is a rare in Chinese population so far. METHODS:The clinical information and blood samples from the patient and his family members were collected and an...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1303
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Isolated cardiac arrhythmia due to a variant in CACNA1C is of recent knowledge. Most reports have been of singleton cases or of quite small families, and estimates of penetrance and expressivity have been difficult to obtain. We here describe a large pedigree, from which such estimates have been calculated. ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.476
更新日期:2019-01-01 00:00:00