scholarly journals Prevalence and cardiometabolic correlates of ketohexokinase gene variants among UK Biobank participants

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247683
Author(s):  
Joseph A. Johnston ◽  
David R. Nelson ◽  
Pallav Bhatnagar ◽  
Sarah E. Curtis ◽  
Yu Chen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Compound Heterozygous ◽  
Gene Variants ◽  
Uk Biobank ◽  
Loss Of Function ◽  
Recessive Condition ◽  
Clinical Consequences ◽  
Autosomal Recessive Condition ◽  
Clinically Significant ◽  
The Uk

Essential fructosuria (EF) is a benign, asymptomatic, autosomal recessive condition caused by loss-of-function variants in the ketohexokinase gene and characterized by intermittent appearance of fructose in the urine. Despite a basic understanding of the genetic and molecular basis of EF, relatively little is known about the long-term clinical consequences of ketohexokinase gene variants. We examined the frequency of ketohexokinase variants in the UK Biobank sample and compared the cardiometabolic profiles of groups of individuals with and without these variants alone or in combination. Study cohorts consisted of groups of participants defined based on the presence of one or more of the five ketohexokinase gene variants tested for in the Affymetrix assays used by the UK Biobank. The rs2304681:G>A (p.Val49Ile) variant was present on more than one-third (36.8%) of chromosomes; other variant alleles were rare (<1%). No participants with the compound heterozygous genotype present in subjects exhibiting the EF phenotype in the literature (Gly40Arg/Ala43Thr) were identified. The rs2304681:G>A (p.Val49Ile), rs41288797 (p.Val188Met), and rs114353144 (p.Val264Ile) variants were more common in white versus non-white participants. Otherwise, few statistically or clinically significant differences were observed after adjustment for multiple comparisons. These findings reinforce the current understanding of EF as a rare, benign, autosomal recessive condition.

scholarly journals A Novel Intronic Pathogenic Variant in STAR With a Dominant Negative Mechanism Causes Attenuated Lipoid Congenital Adrenal Hyperplasia

2021 ◽  
Vol 9 ◽  
pp. 232470962110146
Author(s):  
Erin Finn ◽  
Kimberly Kripps ◽  
Christina Chambers ◽  
Michele Rapp ◽  
Naomi J. L. Meeks ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive ◽  
De Novo ◽  
Dominant Negative ◽  
Adrenal Hyperplasia ◽  
Primary Adrenal Insufficiency ◽  
Heterozygous Variant ◽  
Novel Variant ◽  
Autosomal Recessive Condition ◽  
Clinically Significant

Lipoid congenital adrenal hyperplasia (LCAH) is typically inherited as an autosomal recessive condition. There are 3 reports of individuals with a dominantly acting heterozygous variant leading to a clinically significant phenotype. We report a 46,XY child with a novel heterozygous intronic variant in STAR resulting in LCAH with an attenuated genital phenotype. The patient presented with neonatal hypoglycemia and had descended testes with a fused scrotum and small phallus. Evaluation revealed primary adrenal insufficiency with deficiencies of cortisol, aldosterone, and androgens. He was found to have a de novo heterozygous novel variant in STAR: c.65-2A>C. We report a case of a novel variant and review of other dominant mutations at the same position in the literature. Clinicians should be aware of the possibility of attenuated genital phenotypes of LCAH and the contribution of de novo variants in STAR at c.65-2 to the pathogenesis of that phenotype.

scholarly journals Siblings with Bardet Beidl Syndrome

2013 ◽  
Vol 33 (3) ◽  
pp. 236-238
Author(s):  
Ram Peter ◽  
Priya Jose ◽  
MNG Nair
Keyword(s):  
Clinical Features ◽  
Autosomal Recessive ◽  
Clinical Presentation ◽  
The Body ◽  
Bardet Biedl Syndrome ◽  
Recessive Condition ◽  
Autosomal Recessive Condition

Bardet Biedl syndrome is an autosomal recessive condition affecting many parts of the body. Incidence of BBS is 1 in 100000. Its clinical features varies in person to person though from same family too. We are reporting two siblings with Bardet Beidl syndrome with different clinical presentation. DOI: http://dx.doi.org/10.3126/jnps.v33i3.8081   J. Nepal Paediatr. Soc. 2013;33(3):236-238

Expanding the phenotype of SLC12A6-associated sensorimotor neuropathy

2021 ◽  
Vol 14 (10) ◽  
pp. e244641
Author(s):  
Petya Bogdanova-Mihaylova ◽  
Patricia McNamara ◽  
Sarah Burton-Jones ◽  
Sinéad M Murphy
Keyword(s):  
Corpus Callosum ◽  
Autosomal Recessive ◽  
Sensory Neuropathy ◽  
Rare Condition ◽  
Compound Heterozygous ◽  
Sensorimotor Neuropathy ◽  
Autosomal Recessive Condition ◽  
Solute Carrier ◽  
Compound Heterozygous Mutations ◽  
Clinical Phenotyping

Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a rare autosomal recessive condition characterised by early-onset severe progressive neuropathy, variable degrees of ACC and cognitive impairment. Mutations in SLC12A6 (solute carrier family 12, member 6) encoding the K+–Cl- transporter KCC3 have been identified as the genetic cause of HMSN/ACC. We describe fraternal twins with compound heterozygous mutations in SLC12A6 and much milder phenotype than usually described. Neither of our patients requires assistance to walk. The female twin is still running and has a normal intellect. Charcot-Marie-Tooth Examination Score 2 was 8/28 in the brother and 5/28 in the sister. Neurophysiology demonstrated a length-dependent sensorimotor neuropathy. MRI brain showed normal corpus callosum. Genetic analysis revealed compound heterozygous mutations in SLC12A6, including a whole gene deletion. These cases expand the clinical and genetic phenotype of this rare condition and highlight the importance of careful clinical phenotyping.

scholarly journals Oculotrichodysplasia (OTD): a new probably autosomal recessive condition.

1988 ◽  
Vol 25 (6) ◽  
pp. 430-432 ◽  
Author(s):  
L Cecatto-De-Lima ◽  
M Pinheiro ◽  
N Freire-Maia
Keyword(s):  
Autosomal Recessive ◽  
Recessive Condition ◽  
Autosomal Recessive Condition

Bowel Adenocarcinoma in a Patient with Cystic Fibrosis

1986 ◽  
Vol 31 (2) ◽  
pp. 109-109 ◽  
Author(s):  
J.A. Roberts ◽  
W.M. Tullett ◽  
J. StJ. Thomas ◽  
D. Galloway ◽  
B.H.R. Stack
Keyword(s):  
Cystic Fibrosis ◽  
Adult Male ◽  
Growth And Development ◽  
Autosomal Recessive ◽  
Malignant Tumours ◽  
Live Births ◽  
Bronchopulmonary Infection ◽  
Autosomal Recessive Condition ◽  
Resistance To Infection ◽  
The Uk

Cystic fibrosis (CF) is an autosomal recessive condition affecting one in 2,000 live births in the UK. There are few reports of malignant tumours in this condition probably because, until recently, the majority died before the age of 30 years as a result of recurrent and chronic bronchopulmonary infection with impaired growth and development and resistance to infection due to pancreatic malabsorption. We describe an adult male with CF who died from an adenocarcinoma affecting the ileocaecal region of the bowel.

scholarly journals Characterising SRD5A2 Gene Variants in 37 Indonesian Patients with 5-Alpha-Reductase Type 2 Deficiency

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Nanis S. Marzuki ◽  
Firman P. Idris ◽  
Hannie D. Kartapradja ◽  
Alida R. Harahap ◽  
Jose R. L. Batubara
Keyword(s):  
Autosomal Recessive ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Compound Heterozygous ◽  
Phenotypic Characteristics ◽  
Sex Development ◽  
Srd5a2 Gene ◽  
Diagnostic Approaches ◽  
Autosomal Recessive Condition

The 5-alpha-reductase type 2 deficiency (5ARD2) is an autosomal recessive condition associated with impairment in the conversion of testosterone to dihydrotestosterone. This condition leads to undervirilisation in 46,XY individuals. To date, there have been more than 100 variations identified in the gene responsible for 5ARD2 development (steroid 5-alpha-reductase 2, SRD5A2). However, few studies have examined the molecular characterisation of Indonesian 5ARD2 cases. In the current study, we analysed 37 subjects diagnosed with 46,XY DSD (disorders of sex development) with confirmed variations in the SRD5A2 gene. We examined results from testosterone/dihydrotestosterone (T/DHT) and urinary etiocholanolone/androsterone (Et/An) ratios, as well as from molecular and clinical analyses. Twelve variants in the SRD5A2 gene were identified, and 6 of which were novel, namely, c.34–38delGinsCCAGC, p.Arg50His, p.Tyr136∗, p.Gly191Arg, p.Phe194Ile, and p.Ile253Val variants. Moreover, we determined that 20 individuals contained harmful mutations, while the remaining 17 variants were benign. Those containing harmful mutations exhibited more severe phenotypes with median external genitalia masculinisation scores (EMS) of 3 (1.5–9) and were more likely to be diagnosed at a later age, reared as female, and virilised at pubertal age. In addition, the respective sensitivities for detecting severe 5ARD2 cases using T/DHT (cutoff: 10) and urinary Et/An ratios (cutoff: 0.95) were 85% and 90%, whereas mild cases were only identified with 64.7% and 47.1% sensitivity, respectively. Although we were unable to identify clear correlations between genotypic and phenotypic characteristics in this study, we clearly showed that individuals who were homozygous or compound heterozygous for any of the harmful mutations were more likely to exhibit classic 5ARD2 phenotypes, lower EMS, female assignment at birth, and virilisation during puberty. These results serve to inform the development of improved clinical and molecular 5ARD2 diagnostic approaches, specifically in Indonesian patients.

scholarly journals Bi-allelic SHOC1 loss-of-function mutations cause meiotic arrest and non-obstructive azoospermia

2020 ◽  
pp. jmedgenet-2020-107042
Author(s):  
Chencheng Yao ◽  
Chao Yang ◽  
Liangyu Zhao ◽  
Peng Li ◽  
Ruhui Tian ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Periodic Acid ◽  
Compound Heterozygous ◽  
Obstructive Azoospermia ◽  
Autosomal Recessive Mode ◽  
Loss Of Function ◽  
Meiotic Arrest ◽  
Causative Gene ◽  
Periodic Acid Schiff ◽  
Mode Of Inheritance

BackgroundThe genetic causes of human idiopathic non-obstructive azoospermia (NOA) with meiotic arrest remain unclear.MethodsTwo Chinese families with infertility participated in the study. In family 1, two brothers were affected by idiopathic NOA. In family 2, the proband was diagnosed with idiopathic NOA, and his elder sister suffered from infertility. Whole-exome sequencing (WES) was conducted in the two patients in family 1, the proband in family 2 and 362 additional sporadic patients with idiopathic NOA. Sanger sequencing was used to verify the WES results. Periodic acid–Schiff (PAS), immunohistochemistry (IHC) and meiotic chromosomal spread analyses were carried out to evaluate the stage of spermatogenesis arrested in the affected cases.ResultsWe identified compound heterozygous loss of function (LoF) variants of SHOC1 (c.C1582T:p.R528X and c.231_232del:p.L78Sfs*9, respectively) in both affected cases with NOA from family 1. In family 2, homozygous LoF variant in SHOC1 (c.1194delA:p.L400Cfs*7) was identified in the siblings with infertility. PAS, IHC and meiotic chromosomal spread analyses demonstrated that the spermatogenesis was arrested at zygotene stage in the three patients with NOA. Consistent with the autosomal recessive mode of inheritance, all of these SHOC1 variants were inherited from heterozygous parental carriers. Intriguingly, WES of 362 sporadic NOA cases revealed one additional NOA case with a bi-allelic SHOC1 LoF variant (c.1464delT:p.D489Tfs*13).ConclusionTo the best of our knowledge, this is the first report identifying SHOC1 as the causative gene for human NOA. Furthermore, our study showed an autosomal recessive mode of inheritance in the NOA caused by SHOC1 deficiency.

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