Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Interstitial 4q Deletion Syndrome Including NR3C2 Causing Pseudohypoaldosteronism.

ABSTRACT: Interstitial and terminal deletions of chromosome 4q have been described for many years and have variable phenotypes depending on the size of the deletion present. Clinical features can include developmental delay, growth difficulty, digital differences, dysmorphic features, and cardiac anomalies. Here, we present an infant with pseudohypoaldosteronism found to have a deletion of 4q31.21q31.23, including NR3C2. Heterozygous mutations in NR3C2 have been reported to cause autosomal dominant pseudohypoaldosteronism type 1 (PHA1A). This represents a rare case of PHA1A due to a contiguous interstitial deletion and highlights the importance of evaluating patients with overlapping deletions for PHA1A.

SUBMITTER: Barone Pritchard A

PROVIDER: S-EPMC6995944 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Interstitial 4q Deletion Syndrome Including NR3C2 Causing Pseudohypoaldosteronism.

Barone Pritchard Amanda A Ritter Alyssa A Kearney Hutton M HM Izumi Kosuke K

Molecular syndromology 20191221 6

Interstitial and terminal deletions of chromosome 4q have been described for many years and have variable phenotypes depending on the size of the deletion present. Clinical features can include developmental delay, growth difficulty, digital differences, dysmorphic features, and cardiac anomalies. Here, we present an infant with pseudohypoaldosteronism found to have a deletion of 4q31.21q31.23, including NR3C2. Heterozygous mutations in NR3C2 have been reported to cause autosomal d ...[more]

PMID: 32021607

Similar Datasets

Familial Interstitial 6q23.2 Deletion Including Eya4 Associated With Otofaciocervical Syndrome.

Project description:We report on a 34-year-old woman and her mother who both have clinical features suggestive for otofaciocervical syndrome (OTFCS), a disorder characterized by a combination of facial dysmorphisms, ear abnormalities with hearing loss, and shoulder girdle anomalies. OTFCS presents overlapping features with branchiootorenal spectrum disorders, including branchiootorenal syndrome and branchiootic syndrome. These disorders have been described as clinically distinct entities, but molecular studies have shown that all the causative genes belong to the Pax-Six-Eya-Dach network (PSEDN). So far, the genetic diagnosis of OTFCS has been performed only in very few cases and involves two genes, EYA1 and PAX1; thus, it is likely that other genes have still to be identified. In the present patient, array CGH analysis showed a 3.7-Mb deletion in 6q23; a smaller 1.9-Mb deletion in the same region was detected in her mother. The minimal overlapping region harbors the EYA4 gene. The cases here described are interesting, since they all showed the typical clinical features of OTFCS, associated with a deletion in 6q23.2. Even if we cannot exclude the contribution of other genes to the phenotype, EYA4 is a good candidate for OTFCS according to its pattern of expression, its sequence similarity to EYA1, and its involvement in PSEDN.

| S-EPMC6656857 | biostudies-literature

Interstitial 4q Deletion and Isodicentric Y-Chromosome in a Patient with Dysmorphic Features.

Project description:We present a 2-year-old boy with a de novo 46,XY,idic(Y)(q11.221),del(4)(q26q31.1) karyotype. G-banding, FISH, MLPA, and SNP-array techniques were used to characterize the 24-Mb deletion in 4q and the breakpoint in the isodicentric Y-chromosome region between 15,982,252 and 15,989,842 bp. The patient presented with mild facial dysmorphism, hemangioma, mild frontal cerebral atrophy, and Dandy-Walker variant. Essentially, this case reveals that patients can present more complex genomic imbalances than initially suspected.

| S-EPMC3398833 | biostudies-literature

An infant case of pseudohypoaldosteronism type1A caused by a novel NR3C2 variant.

Project description:Pseudohypoaldosteronism type1A (PHA1A) is the renal form of pseudohypoaldosteronism with autosomal dominant inheritance. PHA1A is caused by haploinsufficiency of the mineralocorticoid receptor, which is encoded by NR3C2. We encountered an infant who was diagnosed with PHA1A due to hyponatremia, hyperkalemia, and poor weight gain in the neonatal period. She carried a novel heterozygous mutation (NM_000901.5: c.1757 + 1 G > C) in the splice donor site of IVS-2 in NR3C2.

| S-EPMC8602301 | biostudies-literature

Two new cases of interstitial 7q35q36.1 deletion including CNTNAP2 and KMT2C.

Project description:BackgroundTerminal deletions of the long arm of chromosome 7 are well known and frequently associated with syndromic holoprosencephaly due to the involvement of the SHH (aliases HHG1, SMMCI, TPT, TPTPS, and MCOPCB5) gene region. However, interstitial deletions including CNTNAP2 (aliases Caspr2, KIAA0868, and NRXN4) and excluding the SHH region are less common.MethodsWe report the clinical and molecular characterization associated with pure 7q35 and 7q35q36.1 deletion in two unrelated patients as detected by oligonucleotide-based array-CGH analysis.ResultsThe common clinical features were abnormal maternal serum screening during first-trimester pregnancy, low occipitofrontal circumference at birth, hypotonia, abnormal feet, developmental delay, impaired language development, generalized seizures, hyperactive behavior, friendly personality, and cranio-facial dysmorphism. Both deletions occurred de novo and sequencing of CNTNAP2, a candidate gene for epilepsy and autism showed absence of mutation on the contralateral allele.ConclusionCombined haploinsufficiency of GALNTL5 (alias GalNAc-T5L), CUL1, SSPO (aliases SCO-spondin, KIAA0543, and FLJ36112), AOC1 (alias DAO), RHEB, and especially KMT2C (alias KIAA1506 and HALR) with monoallelic disruption of CNTNAP2 may explain neurologic abnormalities, hypotonia, and exostoses. Haploinsufficiency of PRKAG2 (aliases AAKG, AAKG2, H91620p, WPWS, and CMH6) and KCNH2 (aliases Kv11.1, HERG, and erg1) genes may be responsible of long QT syndrome observed for one patient.

| S-EPMC8606216 | biostudies-literature

[Clinical and genetic study of an infant with Alagille syndrome: identification of a novel chromosomal interstitial deletion including JAG1 gene].

Project description:Alagille syndrome (ALGS) is an autosomal dominant disease affecting multiple systems including the liver, heart, skeleton, eyes, kidneys and face. This paper reports the clinical and genetic features of an infant with this disease. A 3-month-and-10-day-old female infant was referred to the hospital with jaundiced skin and sclera for 3 months. Physical examination revealed wide forehead and micromandible. A systolic murmur of grade 3-4/6 was heard between the 2th and 3th intercostal spaces on the left side of the sternum. The abdomen was distended, and the liver palpable 3?cm under the right subcostal margin with a medium texture. Serum biochemistry analysis revealed abnormal liver function indices, with markedly elevated bilirubin (predominantly direct bilirubin), total bile acids (TBA) and gamma-glutamyl transpeptidase (GGT). Atrial septal defect and pulmonary stenosis were detected on echocardiography. Next generation sequencing detected entire deletion of the JAG1 gene, and then chromosomal microarray analysis revealed a novel interstitial deletion of 3.0?Mb in size on chr20p12.3p12.2, involving JAG1 gene. The child had special facial features, heart malformations, and cholestasis, and based on the genetic findings, ALGS was definitively diagnosed. Thereafter, symptomatic and supportive treatment was introduced. Thus far, the infant had been followed up till his age of 11 months. The hyperbilirubinemia got improved, but GGT and TBA were persistently elevated, and the long-term outcome needs to be observed. This study extended the JAG1 mutation spectrum, and provided laboratory evidences for the diagnosis and treatment of the patient, and for the genetic counseling and prenatal diagnosis in the family.

| S-EPMC7389279 | biostudies-literature

SORBS2 is a genetic factor contributing to cardiac malformation of 4q deletion syndrome patients.

Project description:Chromosome 4q deletion is one of the most frequently detected genomic imbalance events in congenital heart disease (CHD) patients. However, a portion of CHD-associated 4q deletions without known CHD genes suggests unknown CHD genes within these intervals. Here, we have shown that knockdown of SORBS2, a 4q interval gene, disrupted sarcomeric integrity of cardiomyocytes and caused reduced cardiomyocyte number in human embryonic stem cell differentiation model. Molecular analyses revealed decreased expression of second heart field (SHF) marker genes and impaired NOTCH and SHH signaling in SORBS2-knockdown cells. Exogenous SHH rescued SORBS2 knockdown-induced cardiomyocyte differentiation defects. Sorbs2-/- mouse mutants had atrial septal hypoplasia/aplasia or double atrial septum (DAS) derived from impaired posterior SHF with a similar expression alteration. Rare SORBS2 variants were significantly enriched in a cohort of 300 CHD patients. Our findings indicate that SORBS2 is a regulator of SHF development and its variants contribute to CHD pathogenesis. The presence of DAS in Sorbs2-/- hearts reveals the first molecular etiology of this rare anomaly linked to paradoxical thromboembolism.

| S-EPMC8186900 | biostudies-literature

SORBS2 is a genetic factor contributing to cardiac malformation of 4q deletion syndrome patients.

| S-EPMC8186900 | biostudies-literature

An Interstitial 4q Deletion with a Mosaic Complementary Ring Chromosome in a Child with Dysmorphism, Linear Skin Pigmentation, and Hepatomegaly.

Project description:Interstitial deletions of 4q are rarely reported, vary in size, and have limited genotype-phenotype correlations. Here, genome-wide array CGH analysis identified a 21.6 Mb region of copy number loss at 4q12-q21.1 in a patient diagnosed with dysmorphism, linear skin pigmentation, and hepatomegaly. An additional small ring chromosome was detected in 5/30 cells examined via G-banding. Confirmation of the origin of the ring chromosome was obtained by FISH analysis which identified that the ring chromosome contained material from the deleted region of chromosome 4 and was therefore complementary to the 21.6 Mb deletion. Further microarray studies in the proband using a different microarray platform showed no evidence of mosaicism. This case highlights the importance of an integrated approach to cytogenetic analysis and demonstrates the value of G-banding for detecting mosaicism, as current microarray platforms are unable to detect low level mosaics.

| S-EPMC5551472 | biostudies-other

Novel mutations in the SCNN1A gene causing Pseudohypoaldosteronism type 1.

Project description:Pseudohypoaldosteronism type 1 (PHA1) is a rare inherited disease characterized by resistance to the actions of aldosterone. Mutations in the subunit genes (SCNN1A, SCNN1B, SCNN1G) of the epithelial sodium channel (ENaC) and the NR3C2 gene encoding the mineralocorticoid receptor, result in systemic PHA1 and renal PHA1 respectively. Common clinical manifestations of PHA1 include salt wasting, hyperkalaemia, metabolic acidosis and elevated plasma aldosterone levels in the neonatal period. In this study, we describe the clinical and biochemical manifestations in two Chinese patients with systemic PHA1. Sequence analysis of the SCNN1A gene revealed a compound heterozygous mutation (c.1311delG and c.1439+1G>C) in one patient and a homozygous mutation (c.814_815insG) in another patient, all three variants are novel. Further analysis of the splicing pattern in a minigene construct showed that the c.1439+1G>C mutation can lead to the retainment of intron 9 as the 5'-donor splice site disappears during post-transcriptional processing of mRNA. In conclusion, our study identified three novel SCNN1A gene mutations in two Chinese patients with systemic PHA1.

| S-EPMC3675083 | biostudies-literature

A Neonate with Autosomal Dominant Pseudohypoaldosteronism Type 1 Due to a Novel Microdeletion of the NR3C2 Gene at 4q31.23.

Project description:Dehydration with hyponatremia can occur from a variety of causes and can be potentially fatal to infants. Pseudohypoaldosteronism type 1 (PHA1) is a rare disease that can cause severe dehydration along with hyponatremia and hyperkalemia because of renal tubular unresponsiveness to mineralocorticoids. Autosomal dominant PHA1 (ADPHA1, OMIM #177735) is caused by inactivating mutations in the NR3C2 gene, which encodes the mineralocorticoid receptor, and it can lead to renal salt-wasting, dehydration, and failure to thrive during infancy. Here, we report a case of a 20-day-old female neonate who presented as severe dehydration with hyponatremia and polyuria. We suspected that her diagnosis might be PHA1 based on markedly elevated plasma renin activity and serum aldosterone levels. For the genetic diagnosis of PHA1, we performed targeted exome sequencing of all causative genes of PHA1, but the result was negative. We confirmed by chromosomal microarray that a novel heterozygous microdeletion was found in the 4q31.23 region spanning exons 7-9 of the NR3C2 gene, and the patient was diagnosed with ADPHA1. In conclusion, our patient is a case of ADPHA1 that developed into a salt-wasting crisis in the neonatal period due to a microdeletion of the 4q31.23 region inherited from her father.

| S-EPMC8700017 | biostudies-literature