scholarly journals A new allelic variant of periventricular nodular heterotopia type 7 in a patient with adrenogenital syndrome due to a 21-hydroxylase deficiency

2019 ◽  
pp. 50-56
Author(s):  
Е.Л. Дадали ◽  
Т.В. Маркова ◽  
А.О. Боровиков ◽  
А.Л. Чухрова ◽  
Н.Н. Вассерман ◽  
...  
Keyword(s):  
De Novo ◽  
Speech Development ◽  
Monogenic Disease ◽  
Homozygous Mutation ◽  
Hydroxylase Deficiency ◽  
Adrenogenital Syndrome ◽  
Periventricular Nodular Heterotopia ◽  
Monogenic Diseases ◽  
Nodular Heterotopia ◽  
21 Hydroxylase Deficiency

Представлено описание клинико-генетических характеристик ребенка 2 лет с двумя моногенными заболеваниями: сольтеряющей формой адрено--генитального синдрома с аутосомно-рецессивным типом наследования и узловой гетеротопий мозга 7 типа, наследующейся аутосомно-доминантно, диагностированных с использованием двух различных молекулярно-генетических методов. Наличие адрено-генитального синдрома диагностировано в первые дни жизни на основании типичных клинических проявлений и подтверждено путём прямой ДНК-диагностики, в результате которой обнаружена гомозиготная мутация p.R356W в гене CYP21А2. Наличие второго моногенного заболевания предполагалось на основании диагностики грубой задержки психомоторного и речевого развития и аномалий строения головного мозга, обнаруженных при проведении магнитно-резонансной томографии. При секвенировании клинического экзома выявлена ранее не описанная нуклеотидная замена с.2015С>T (р.W672I) в гене NEDD4L. Патогенные варианты в домене HECT данного белка приводят к перивентрикулярной узловой гетеротопии 7 типа (OMIM:617021). Анализ данного варианта методом прямого секвенирования по Сэнгеру в семье показал его происхождение de novo. We report 2-year-old girl with two monogenic diseases - adrenogenital syndrome with autosomal recessive inheritance mode and periventricular nodular heterotopia type 7 with autosomal dominant, diagnosed by two different molecular genetic methods. The presence of adreno-genital syndrome diagnosed in the first days of life based on typical clinical manifestations and the homozygous mutation was detected p.R356Wby direct DNA testing CYP21А2 gene. The presence of the second monogenic disease was proposed base on the observation the severe delay of psychomotor and speech development and abnormalities of the brain structure detected by MRI. Clinical exome sequencing identified previously not described single nucleotide substitution c.2015С>T (p.W672I) in NEDD4L gene. Pathogenic variants in HECT domain of this protein lead to periventricular nodular heterotopia type 7 (OMIM:617021). Analysis of segregation this variant in the family by direct sequencing of Sanger showed its origin de novo.

DIFFICULTIES IN THE DIAGNOSIS OF THE ADRENOGENITAL SYNDROME IN INFANCY

PEDIATRICS ◽  
1972 ◽  
Vol 49 (2) ◽  
pp. 198-205
Author(s):  
C. H. Shackleton ◽  
F. L. Mitchell ◽  
J. W. Farquhar
Keyword(s):  
Hydroxylase Deficiency ◽  
Adrenogenital Syndrome ◽  
Steroid Excretion ◽  
21 Hydroxylase Deficiency ◽  
Hydroxy Steroid ◽  
Steroid Dehydrogenase

Pregnanetriol was not excreted by an infant (7 days old) who was later shown to have a defect in steroid 21-hydroxylase. However, the excretion of this compound increased during the following days (1.2 mg on the thirteenth day of life). A high excretion of 3β-hydroxy-Δ steroids was the most noticeable abnormality in steroid excretion noted on the seventh day of life (e.g., 3β, 16α-dihydroxy-5-pregnen-20-one, 15 mg; 3β, 21-dihydroxy-5-pregnen-20-one, 1.4 mg and 3β, 16α-dihydroxy-5-androsten-17-one, 7.4 mg). This high 3β-hydroxy-Δ steroid excretion results in difficulties in distinguishing a defect in 3β-hydroxy steroid dehydrogenase from a 21-hydroxylase deficiency. At the age of 14 months the principal steroids excreted were those predominant in other cases of 21-hydroxylase deficiency, viz. pregnanetriol and 5β-pregnane-3α, 17α, 20α-triol-11-one (11-oxo-pregnanetriol).

scholarly journals A Case of Salt-Wasting Congenital Adrenal Hyperplasia with Triple Homozygous Mutation: Review of Literature

2020 ◽  
Author(s):  
Maria Laura Iezzi ◽  
Gaia Varriale ◽  
Luca Zagaroli ◽  
Stefania Lasorella ◽  
Marco Greco ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive ◽  
Homozygous Mutation ◽  
Adrenal Hyperplasia ◽  
Phenotype Correlation ◽  
Hydroxylase Deficiency ◽  
Autosomal Recessive Disorders ◽  
Salt Wasting ◽  
21 Hydroxylase Deficiency ◽  
Recessive Disorders

AbstractCongenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency represents a group of autosomal recessive disorders characterized by impaired cortisol production due to altered upstream steroid conversions, subclassified as classic and nonclassic forms. The genotype–phenotype correlation is possible in the most frequent case but not in all. Despite in literature many mutations are known, there is the possibility of finding a new genetic pattern in patients with CAH.

scholarly journals Hemizygous FLNA variant in West syndrome without periventricular nodular heterotopia

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Yoshitaka Hiromoto ◽  
Yoshiteru Azuma ◽  
Yuichi Suzuki ◽  
Megumi Hoshina ◽  
Yuri Uchiyama ◽  
...  
Keyword(s):  
De Novo ◽  
Missense Variant ◽  
West Syndrome ◽  
Periventricular Nodular Heterotopia ◽  
Psychomotor Delay ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Epileptic Patients ◽  
Nodular Heterotopia ◽  
Refractory Seizures

AbstractPathogenic FLNA variants can be identified in patients with seizures accompanied by periventricular nodular heterotopia (PVNH). It is unusual to find FLNA aberrations in epileptic patients without PVNH on brain imaging. We report a boy with cryptogenic West syndrome followed by refractory seizures and psychomotor delay. We performed whole-exome sequencing and identified a de novo missense variant in FLNA. It is noteworthy that this patient showed no PVNH. As no other pathogenic variants were found in epilepsy-related genes, this FLNA variant likely caused West syndrome but with no PVNH.

The prevalence of the non-classical form of congenital adrenal hyperplasia as exemplified (by the population of the Moscow region)

2013 ◽  
Vol 59 (4) ◽  
pp. 18-22
Author(s):  
T A Ionova ◽  
A N Tiul'pakov ◽  
S G Kalinenkova
Keyword(s):  
Neonatal Screening ◽  
Moscow Region ◽  
Hydroxylase Deficiency ◽  
Classical Form ◽  
True Incidence ◽  
Monogenic Diseases ◽  
Frequent Mutations ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Autosomal Recessive Pattern

The non-classical form of 21-hydroxylase deficiency (NC21OH) is one of the most common monogenic diseases inherited in the autosomal-recessive pattern. The incidence of this condition in the Russian population, unlike that of its classical variant, remains to be elucidated. Aim. The objective of the present study was to estimate the true incidence of NC21OH based on the prevalence of the two most frequent mutations associated with this disease. A total of 998 randomly selected blood spots were obtained in the course of neonatal screening of the children born within one calendar year at the territory of the Moscow region. The incidence of the disease was calculated with the use of Hardi-Weinberg equation. The minimal prevalence rate of NC21OH in the population of the Moscow region was estimated to be 1:2206. The level of 17-hydroxyprogesterone (17-OHP) calculated based on the results of the screening studies can not be used to identify the carriers of the pathology of interest whereas neonatal screening allows to diagnose no more than 90% of the cases of NC21OH.

scholarly journals Genesis by meiotic unequal crossover of a de novo deletion that contributes to steroid 21-hydroxylase deficiency.

1990 ◽  
Vol 87 (6) ◽  
pp. 2107-2111 ◽  
Author(s):  
P. Sinnott ◽  
S. Collier ◽  
C. Costigan ◽  
P. A. Dyer ◽  
R. Harris ◽  
...  
Keyword(s):  
De Novo ◽  
Hydroxylase Deficiency ◽  
Unequal Crossover ◽  
21 Hydroxylase Deficiency

scholarly journals De novo and inherited private variants in MAP1B in periventricular nodular heterotopia

PLoS Genetics ◽  
2018 ◽  
Vol 14 (5) ◽  
pp. e1007281 ◽  
Author(s):  
Erin L. Heinzen ◽  
Adam C. O'Neill ◽  
Xiaolin Zhu ◽  
Andrew S. Allen ◽  
Melanie Bahlo ◽  
...  
Keyword(s):  
De Novo ◽  
Periventricular Nodular Heterotopia ◽  
Nodular Heterotopia

scholarly journals Divergent Phenotype of Two Siblings Human Leukocyte Antigen Identical, Affected by Nonclassical and Classical Congenital Adrenal Hyperplasia Caused by 21-Hydroxylase Deficiency

2006 ◽  
Vol 91 (11) ◽  
pp. 4510-4513 ◽  
Author(s):  
O. Porzio ◽  
V. Cunsolo ◽  
M. Malaponti ◽  
E. De Nisco ◽  
A. Acquafredda ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Human Leukocyte Antigen ◽  
De Novo ◽  
Human Leukocyte ◽  
Compound Heterozygote ◽  
Variable Degree ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Leukocyte Antigen ◽  
21 Hydroxylase Deficiency

Abstract Context: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders most often caused by enzyme 21-hydroxylase deficiency. Most mutations causing enzymatic deficiency are generated by recombinations between the active gene CYP21 and the pseudogene CYP21P. Only 1–2% of affected alleles result from spontaneous mutations. The phenotype of CAH varies greatly, usually classified as classical or nonclassical, depending on variable degree in 21-hydroxylase activity. Here we report a divergent phenotype of two human leukocyte antigen identical siblings, affected by nonclassical and classical CAH caused by 21-hydroxylase deficiency due to different genotype. Patients and Methods: Using direct sequencing method and Southern blot, we studied two children (one male and one female), affected, respectively, by nonclassical and classical CAH and their parents. Results: The mother was heterozygous for the Q318X mutation, and the father was heterozygous for the V281L mutation. The brother was a compound heterozygote for the mutations V281L and Q318X, whereas the proband was compound heterozygote for the Q318X mutation and a large conversion. The two children are human leukocyte antigen identical (A*02;B*14;DRB1*01/A*33;B*14;DRB1*03). Conclusions: Different phenotype of the proband is the result of compound heterozygosity for the maternal mutation Q318X and a de novo large conversion.

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