Patients with Thyroid Dyshormonogenesis and Variants: Molecular and Clinical Description and Genotype-Phenotype Correlation.

Thyroid dyshormonogenesis (THD) is a heterogeneous group of genetic diseases caused by the total or partial defect in the synthesis or secretion of thyroid hormones. Genetic variants in can cause partial to total iodination organification defects and clinical heterogeneity, from transient to permanent congenital hypothyroidism. The aim of this study was to undertake a molecular characterization and genotype-phenotype correlation in patients with THD and candidate variants in .

Clinical and molecular study of patients with thyroid dyshormogenesis and variants in the gene.

Introduction: Defects in any thyroid hormone synthesis steps cause thyroid dyshormonogenesis (THD). THD due to () gene variants is a cause of congenital hypothyroidism (CH) with a wide clinical spectrum, ranging from mild to severe permanent hypothyroidism. We present high-throughput sequencing results of patients with variants.

Primary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel Variant and Possible Modifier Gene.

We report a novel missense variant co-segregated with a familial X-linked retinitis pigmentosa (XLRP) case. The brothers were hemizygous for this variant, but only the proband presented with primary ciliary dyskinesia (PCD). Thus, we aimed to elucidate the role of the variant and other modifier genes in the phenotypic variability observed in the family and its impact on motile cilia.

Genetics and Natural History of Non-pancreatectomized Patients With Congenital Hyperinsulinism Due to Variants in ABCC8.

Context: Patients with congenital hyperinsulinism due to ABCC8 variants generally present severe hypoglycemia and those who do not respond to medical treatment typically undergo pancreatectomy. Few data exist on the natural history of non-pancreatectomized patients.

Objective: This work aims to describe the genetic characteristics and natural history in a cohort of non-pancreatectomized patients with congenital hyperinsulinism due to variants in the ABCC8 gene.

Novel variant in as a cause of different sex development with partial gonadal dysgenesis associated with microcephaly, eye defects, and distal phalangeal hypoplasia of both thumbs: Case report.

The palmitoylation of the Hedgehog (Hh) family of morphogens, named sonic hedgehog (SHH), desert hedgehog (DHH), and Indian hedgehog (IHH), is crucial for effective short- and long-range signaling. The hedgehog acyltransferase (HHAT) attaches the palmitate molecule to the Hh; therefore, variants in cause a broad spectrum of phenotypes. A missense novel variant c.

Incidence and Prevalence of Children's Diffuse Lung Disease in Spain.

Background: Children's diffuse lung disease, also known as children's Interstitial Lung Diseases (chILD), are a heterogeneous group of rare diseases with relevant morbidity and mortality, which diagnosis and classification are very complex. Epidemiological data are scarce. The aim of this study was to analyse incidence and prevalence of chILD in Spain.

Seventy eight children born small for gestational age without catch-up growth treated with growth hormone from the prepubertal stage until adult height age. An evaluation of puberty and changes in the metabolic profile.

Unlabelled: A wide variation in height gain rate is observed in children small for gestational age (SGA) treated with growth hormone (GH). The aim of this study was to evaluate prepubertal and pubertal growth, height gain attained at adult age and to assess potential predictive factors in catch-up growth. Changes in metabolic profile were also analyzed.

Seventy eight children born small for gestational age without catch-up growth treated with growth hormone from the prepubertal stage until adult height age. An evaluation of puberty and changes in the metabolic profile.

Unlabelled: A wide variation in height gain rate is observed in children small for gestational age (SGA) treated with growth hormone (GH). The aim of this study was to evaluate prepubertal and pubertal growth, height gain attained at adult age and to assess potential predictive factors in catch-up growth. Changes in metabolic profile were also analyzed.

Immunofluorescence Analysis as a Diagnostic Tool in a Spanish Cohort of Patients with Suspected Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by an alteration of ciliary structure. Immunofluorescence, consisting in the detection of the presence and distribution of cilia proteins in human respiratory cells by fluorescence, has been recently proposed as a technique to improve understanding of disease-causing genes and diagnosis rate in PCD. The objective of this study is to determine the accuracy of a panel of four fluorescently labeled antibodies (DNAH5, DNALI1, GAS8 and RSPH4A or RSPH9) as a PCD diagnostic tool in the absence of transmission electron microscopy analysis.

Phenotypic Variability of Patients With PAX8 Variants Presenting With Congenital Hypothyroidism and Eutopic Thyroid.

Purpose: Thyroid dyshormonogenesis is a heterogeneous group of hereditary diseases produced by a total/partial blockage of the biochemical processes of thyroid-hormone synthesis and secretion. Paired box 8 (PAX8) is essential for thyroid morphogenesis and thyroid hormone synthesis. We aimed to identify PAX8 variants in patients with thyroid dyshormonogenesis and to analyze them with in vitro functional studies.

Broad Phenotypes of Disorders/Differences of Sex Development in Patients Through Oligogenic Disease.

Disorders/differences of sex development (DSD) are the result of a discordance between chromosomal, gonadal, and genital sex. DSD may be due to mutations in any of the genes involved in sex determination and development in general, as well as gonadal and/or genital development specifically. is one of the recognized DSD genes.

A Novel Homozygous AMRH2 Gene Mutation in a Patient with Persistent Müllerian Duct Syndrome.

Persistent müllerian duct syndrome (PMDS) is characterized by the presence of müllerian duct derivatives in otherwise phenotypically normal males. Homozygous or compound heterozygous alterations in AMH or AMHR2 have been identified in approximately 88% of PMDS cases. We report on a male patient with bilateral undescended gonads, müllerian derivatives, and normal serum AMH levels.

Isolated pulmonary interstitial glycogenosis associated with alveolar growth abnormalities: A long-term follow-up study.

Introduction: Pulmonary interstitial glycogenosis (PIG) is a rare infant interstitial lung disease characterized by an increase in the number of interstitial mesenchymal cells, presenting as enhanced cytoplasmic glycogen, and is considered to represent the expression of an underlying lung development disorder.

Methods: This study describes the clinical, radiological, and functional characteristics and long-term outcomes (median 12 years) of nine infants diagnosed with isolated PIG associated with alveolar simplification in the absence of other diseases.

Results: All patients presented with tachypnea.

Broad phenotypes in heterozygous NR5A1 46,XY patients with a disorder of sex development: an oligogenic origin?

SF-1/NR5A1 is a transcriptional regulator of adrenal and gonadal development. NR5A1 disease-causing variants cause disorders of sex development (DSD) and adrenal failure, but most affected individuals show a broad DSD/reproductive phenotype only. Most NR5A1 variants show in vitro pathogenic effects, but not when tested in heterozygote state together with wild-type NR5A1 as usually seen in patients.

Mechanism of the Dual Activities of Human CYP17A1 and Binding to Anti-Prostate Cancer Drug Abiraterone Revealed by a Novel V366M Mutation Causing 17,20 Lyase Deficiency.

The gene regulates sex steroid biosynthesis in humans through 17α-hydroxylase/17,20 lyase activities and is a target of anti-prostate cancer drug abiraterone. In a 46, XY patient with female external genitalia, together with a loss of function mutation S441P, we identified a novel missense mutation V366M at the catalytic center of CYP17A1 which preferentially impaired 17,20 lyase activity. Kinetic experiments with bacterially expressed proteins revealed that V366M mutant enzyme can bind and metabolize pregnenolone to 17OH-pregnenolone, but 17OH-pregnenolone binding and conversion to dehydroepiandrosterone (DHEA) was impaired, explaining the patient’s steroid profile.

GATA4 Variants in Individuals With a 46,XY Disorder of Sex Development (DSD) May or May Not Be Associated With Cardiac Defects Depending on Second Hits in Other DSD Genes.

Disorders of sex development (DSD) consist of a wide range of conditions involving numerous genes. Nevertheless, about half of 46,XY individuals remain genetically unsolved. gene variants, mainly related to congenital heart defects (CHD), have also been recently associated with 46,XY DSD.

A rare cause of primary adrenal insufficiency due to a homozygous Arg188Cys mutation in the gene.

Unlabelled: Steroidogenic acute regulatory protein () is a key protein for the intracellular transport of cholesterol to the mitochondrium in endocrine organs (e.g. adrenal gland, ovaries, testes) and essential for the synthesis of all steroid hormones.

[Body mass index and tri-ponderal mass index of 1,453 healthy non-obese, non-undernourished millennial children. The Barcelona longitudinal growth study].

Introduction: Body mass index-for age (BMI) and tri-ponderal mass index-for-age (TMI) values of healthy non-underweight, non-obese millennial children have not been reported until now. We aimed to obtain these values.

Subjects And Methods: Longitudinal growth study (1995-2017) of 1,453 healthy non-underweight, non-obese millennial children, from birth (n = 477) or from 4 years of age (n = 976) to 18 years in girls and 19 years in boys (25,851 anthropometric measurements).