scholarly journals Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation Is a Novel Defect in Thyroid Dyshormonogenesis

2018 ◽  
Vol 103 (5) ◽  
pp. 1889-1898 ◽  
Author(s):  
Minjing Zou ◽  
Ali S Alzahrani ◽  
Ali Al-Odaib ◽  
Mohammad A Alqahtani ◽  
Omer Babiker ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Congenital Hypothyroidism ◽  
Screening Program ◽  
Genetic Defects ◽  
Newborn Screening Program ◽  
Endocrine Disorder ◽  
Thyroid Dysgenesis ◽  
Thyroid Dyshormonogenesis ◽  
Biallelic Mutations ◽  
Saudi Patients

Abstract Context Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, affecting one in 3000 to 4000 newborns. Since the introduction of a newborn screening program in 1988, more than 300 cases have been identified. The underlying genetic defects have not been systematically studied. Objective To identify the mutation spectrum of CH-causing genes. Methods Fifty-five patients from 47 families were studied by next-generation exome sequencing. Results Mutations were identified in 52.7% of patients (29 of 55) in the following 11 genes: TG, TPO, DUOX2, SLC26A4, SLC26A7, TSHB, TSHR, NKX2-1, PAX8, CDCA8, and HOXB3. Among 30 patients with thyroid dyshormonogenesis, biallelic TG mutations were found in 12 patients (40%), followed by biallelic mutations in TPO (6.7%), SLC26A7 (6.7%), and DUOX2 (3.3%). Monoallelic SLC26A4 mutations were found in two patients, one of them coexisting with two tandem biallelic deletions in SLC26A7. In 25 patients with thyroid dysgenesis, biallelic mutations in TSHR were found in six patients (24%). Biallelic mutations in TSHB, PAX 8, NKX2-1, or HOXB3 were found once in four different patients. A monoallelic CDCA8 mutation was found in one patient. Most mutations were novel, including three TG, two TSHR, and one each in DUOX2, TPO, SLC26A7, TSHB, NKX2-1, PAX8, CDCA8, and HOXB3. SLC26A7 and HOXB3 were novel genes associated with thyroid dyshormonogenesis and dysgenesis, respectively. Conclusions TG and TSHR mutations are the most common genetic defects in Saudi patients with CH. The prevalence of other disease-causing mutations is low, reflecting the consanguineous nature of the population. SLC26A7 mutations appear to be associated with thyroid dyshormonogenesis.

scholarly journals The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes

2018 ◽  
Vol 178 (6) ◽  
pp. 623-633 ◽  
Author(s):  
Feng Sun ◽  
Jun-Xiu Zhang ◽  
Chang-Yi Yang ◽  
Guan-Qi Gao ◽  
Wen-Bin Zhu ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Congenital Hypothyroidism ◽  
Autosomal Recessive Inheritance ◽  
Chinese Patients ◽  
Compound Heterozygous ◽  
Genetic Characteristics ◽  
Thyroid Dysgenesis ◽  
Hormone Synthesis ◽  
Thyroid Dyshormonogenesis ◽  
Biallelic Mutations

Objective Congenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited. Design and methods One hundred ten patients with primary CH were recruited in this study. All exons and exon–intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees. Results Our results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes (DUOX2, DUOXA2, DUOXA1, TG, TPO and TSHR) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2, DUOXA2, TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes (FOXE1, NKX2-1, PAX8 and HHEX) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands. Conclusions Most cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.

scholarly journals Incidence and Interrelated Factors in Patients With Congenital Hypothyroidism as Detected by Newborn Screening in Guangxi, China

2015 ◽  
Vol 2 ◽  
pp. 2333794X1456719 ◽  
Author(s):  
Xin Fan ◽  
Shaoke Chen ◽  
Jiale Qian ◽  
Suren Sooranna ◽  
Jingi Luo ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
Screening Program ◽  
Thyroid Stimulating Hormone ◽  
Who Guidelines ◽  
Newborn Screening Program ◽  
Study Results ◽  
Stimulating Hormone

Background. A newborn screening program (NSP) for congenital hypothyroidism (CH) was carried out in Guangxi in order to understand the incidence of CH and the factors interrelated to major types of CH in this region of China. Methods. During 2009 to 2013, data from 930 612 newborns attending NSP in Guangxi were collected. Patients were classified with either permanent CH (PCH) or transient CH (TCH) after 2 years of progressive study. Results. A total of 1210 patients were confirmed with CH with an incidence of 1/769, including 68 PCH and 126 TCH cases with incidences of 1/6673 and 1/3385, respectively. The frequency of thyroid stimulating hormone values greater than 5 mIU/L was 7.2%, which, based on WHO guidelines, suggests that the population was mildly iodine deficient. Conclusions. The incidence of CH was high in Guangxi. Approximately two thirds of CH patients were TCH, which may be due to a deficiency in iodine within the population.

scholarly journals Incidence of congenital hypothyroidism in the city of Uberaba/Minas Gerais and etiological evaluation of the affected subjects

2012 ◽  
Vol 56 (5) ◽  
pp. 305-312 ◽  
Author(s):  
Heloísa Marcelina da Cunha Palhares ◽  
Lilian Carla Silva ◽  
Luciene Mayumi Sato ◽  
Beatriz Hallal Jorge Lara ◽  
Sybele de Souza Castro Miranzi ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Screening Program ◽  
Minas Gerais ◽  
The State ◽  
Thyroid Dysgenesis ◽  
Outpatient Unit ◽  
Transient Hypothyroidism ◽  
Molecular Studies ◽  
Definition Of ◽  
The City

OBJECTIVE: The objective of this study was to determine the incidence and etiology of congenital hypothyroidism (CH) in Uberaba, MG. SUBJECTS AND METHODS: From 2001 to 2010, by reviewing patient files from a public reference outpatient unit. The screening program covered 88% of live-born children. RESULTS: CH was diagnosed in 16 children, representing an incidence of 1:2,017 live-born children screened. The etiological evaluation was done in 15 children and revealed seven cases of thyroid dysgenesis, seven of dyshormonogenesis, and one case of transient hypothyroidism. One child moved away from the state before etiological investigation was carried out. CONCLUSION: We concluded that both the incidence of CH and of dyshormonogenesis as the main causes of CH were increased in the investigated region, but molecular studies are necessary for a better definition of etiology.

scholarly journals Phenylketonuria, congenital hypothyroidism and haemoglobinopathies: public health issues for a Brazilian newborn screening program

2012 ◽  
Vol 28 (9) ◽  
pp. 1623-1631 ◽  
Author(s):  
Judy Botler ◽  
Luiz Antonio Bastos Camacho ◽  
Marly Marques da Cruz
Keyword(s):  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
Screening Program ◽  
Ethnic Composition ◽  
Health Issues ◽  
Newborn Screening Program ◽  
Cell Disease ◽  
Laboratory Methods ◽  
Detection Coverage

In this study, the frequency of detected congenital hypothyroidism, phenylketonuria and haemoglobinopathies in the State of Rio de Janeiro's (Brazil) Newborn Screening Program (NBSP) was analyzed between the years of 2005 and 2007. There were two Newborn Screening Reference Centers (named NSRC A and B) with programmatic differences. In 2007, overall detection coverage reached 80.7%. The increase in the incidence of congenital hypothyroidism (1:1,030 in 2007) was attributed to the reduction of neonatal TSH value limits over time. The incidence discrepancy of phenylketonuria between NSRC A (1:28,427) and B (1:16,522) might be partially explained by the small number of cases. The incidence of sickle cell disease and its traits were uniformly high (1:1,288 and 1:21, respectively). This was coherent with the ethnic composition of the population. The differences in laboratory methods and critical values, in addition to other programmatic issues, may explain the variances in the results and limited analysis of the role of biological and environmental determinants in the occurrence of these diseases.

scholarly journals Natural course of congenital hypothyroidism by dual oxidase 2 mutations from the neonatal period through puberty

2016 ◽  
Vol 174 (4) ◽  
pp. 453-463 ◽  
Author(s):  
Yoshihiro Maruo ◽  
Keisuke Nagasaki ◽  
Katsuyuki Matsui ◽  
Yu Mimura ◽  
Asami Mori ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Screening Program ◽  
Direct Sequencing ◽  
Japanese Patients ◽  
Psychomotor Development ◽  
Thyroid Peroxidase ◽  
Maturation Factor ◽  
Dual Oxidase ◽  
Novel Alleles ◽  
Biallelic Mutations

AimWe previously reported that biallelic mutations in dual oxidase 2 (DUOX2) cause transient hypothyroidism. Since then, many cases with DUOX2 mutations have been reported. However, the clinical features and prognosis of individuals with DUOX2 defects have not been clarified.ObjectiveWe investigated the prognosis of patients with congenital hypothyroidism (CH) due to DUOX2 mutations.PatientsTwenty-five patients were identified by a neonatal screening program and included seven familial cases. Their serum TSH values ranged from 18.9 to 734.6 mU/l. Twenty-two of the patients had low serum free thyroxine (fT4) levels (0.17–1.1 ng/dl). Twenty-four of the patients were treated with L-thyroxine.MethodsWe analyzed the DUOX2, thyroid peroxidase, Na+/I− symporter, and dual oxidase maturation factor 2 genes of these 25 patients by PCR-amplified direct sequencing. An additional 11 genes were analyzed in 11 of the 25 patients using next-generation sequencing.ResultsAll patients had biallelic DUOX2 mutations, and seven novel alleles were detected. Fourteen of the patients were able to discontinue replacement therapy, and seven were receiving reduced L-thyroxine doses. Normalization of thyroglobulin lagged several years behind the completion of treatment. Two patients showed permanent hypothyroidism. Except for one case of a learning disability, growth and psychomotor development were normal.ConclusionThe prognosis of Japanese patients with DUOX2 defects was usually transient CH. Delayed improvement of thyroglobulin indicates that these patients have subclinical hypothyroidism. Hypothyroidism did not recur in patients during the study period (up to 18 years old).

scholarly journals MON-101 Costa Rican National Primary Congenital Hypothyroidism Screening Program Evaluation. Retrospective Cohort Trial Between 2015 and 2017

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Alejandro Cob ◽  
Fred Cavallo Aita ◽  
Agnes Rodríguez
Keyword(s):  
Newborn Screening ◽  
Sensitivity And Specificity ◽  
Congenital Hypothyroidism ◽  
Clinical Evaluation ◽  
Screening Test ◽  
Screening Program ◽  
Costa Rican ◽  
International Standards ◽  
Newborn Screening Program ◽  
The Third

Abstract Congenital hypothyroidism (CH) is one of the leading causes of intellectual impairment worldwide in infancy. The newborn screening has been able to prevent this mental disability, by a prompt initiation of therapy. Over the last years the incidence of HC has been increasing, mainly by lowering the screening cut-off level that leads to detection of milder cases. There is conflicting evidence if children with mild CH without treatment may develop neurological impairment in the future. Costa Rican newborn screening program in divided in three stages, measuring serum TSH concentrations from a heel prick aliquot of capillary blood dried onto a filter paper. Each test has different TSH cut-off values to determine if the newborn needs a clinical evaluation by an endocrinologist, needs another screening test or rules out hypothyroidism. We developed an observational, descriptive, retrospective study, based on medical records, to evaluate our newborn screening program performance. The study included the total national population of screened newborns from 2015 to 2017. Descriptive analysis and analytical analysis of variables were done, and test’s sensitivity and specificity were determined. The study analyzed 204.241 screened newborns, and 145 children referred to the Endocrinology Department of the National Children Hospital. This population represents 97% of births in these 3 years. The recall rate for a first positive test was 0.3%. Congenital hypothyroidism was confirmed in 73% of children referred to the Endocrinology Department because of a positive screening. Incidence was 1/1926 births. Detection rate was independent of birth weight nor gestational age. 45.3% of children diagnosed with CH were detected after the first screening test, 52.8% after the second screening test and 1.9% after the third screening test. Screening test analysis showed high sensitivity and specificity, with diagnostic accuracy above 90%, except for the third screening test. Free thyroxine measurements alone weren’t useful to predict CH diagnosis. The coverage of the national neonatal screening program extends almost to the entire population. Our test specificity is within international standards. Incidence of CH in Costa Rica is similar to that reported in medical literature. With current detection cut-off level, there is no need of performing a second mandatory evaluation to preterm and low weight newborns. The third screening test has a low performance rate, does not improve detection of children with CH significantly, and delays clinical evaluation by the endocrinologist. Prognosis of treated children with CH is excellent, with no evidence of severe cognitive deficit.

α-Fetoprotein and Hypothyroidism in Infants

PEDIATRICS ◽  
1992 ◽  
Vol 90 (6) ◽  
pp. 1008-1009
Author(s):  
G. J. MIZEJEWSKI ◽  
K. A. PASS
Keyword(s):  
New York ◽  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
Screening Program ◽  
New York State ◽  
Elevated Serum ◽  
Thyroid Stimulating Hormone ◽  
Newborn Screening Program ◽  
Newborn Period ◽  
York State

To the Editor.— We recently have documented a relationship between serum α-fetoprotein (AFP) and congenital hypothyroidism (CH) in the newborn period. Previous studies in our laboratory and others had reported a relationship between elevated serum AFP and elevated thyroid-stimulating hormone (TSH)/low thyroxine T4 in newborns and infants in the first few months of life.1-4 The New York State Newborn Screening Program for CH routinely screens more than 300 000 specimens per year diagnosing 120 to 140 confirmed cases of CH annually.

scholarly journals Incidence of congenital hypothyroidism in China: data from the national newborn screening program, 2013–2015

2018 ◽  
Vol 31 (6) ◽  
pp. 601-608 ◽  
Author(s):  
Kui Deng ◽  
Chunhua He ◽  
Jun Zhu ◽  
Juan Liang ◽  
Xiaohong Li ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
Screening Program ◽  
Thyroid Stimulating Hormone ◽  
Coastal Areas ◽  
Newborn Screening Program ◽  
Geographical Variations ◽  
Potential Association ◽  
Incidence Risk ◽  
Epidemiological Characteristics

Abstract Background: Congenital hypothyroidism (CH) is one of the most frequent, preventable causes of mental retardation. Little has been reported on the epidemiological characteristics of CH in China. We aimed to estimate the incidence of CH in China and investigate its geographical variation. Methods: We analyzed data from the nationwide newborn screening program for CH between 2013 and 2015. Poisson regression was used to generate the odds ratios (ORs) and 95% confidence intervals (CIs) between the rates of CH and selected demographic characteristics and assess the potential association between CH incidence and geographical locations. Results: A total of 18,666 patients with CH were identified from 45.2 million newborns, yielding an overall incidence rate of 4.13 per 10,000 live births. Compared with those in the remote area, regardless of infant sex, a higher incidence risk for CH was present in newborns in coastal areas and inland areas (females: OR=2.00, 95% CI: 1.86–2.16 and OR=1.74, 95% CI: 1.61–1.87, respectively; males: OR=1.70, 95% CI: 1.59–1.83 and OR=1.52, 95% CI: 1.42–1.63, respectively). Additionally, the highest risk of CH for thyroid-stimulating hormone (TSH) screening values <40 mU/L was observed among neonates in the coastal areas, while TSH screening values of 70–100 mU/L were observed among those in the inland areas. Conclusions: The overall incidence of CH is high in China. The significant geographical variations of CH incidence are presented in this study.

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