In addition, one patient presented with nephroblastoma. The possible involvement of QRICH1 in pediatric cancer assumes careful surveillance a key priority for outcome of these patients. [physiciansweekly.com]

Neither variant was present in the gnomAD database. In vitro studies showed that the R536X variant resulted in decreased protein expression, suggesting haploinsufficiency. [findzebra.com]

Here, we present four unrelated individuals with one known nonsense variant (c.1954C > T; p.[Arg652*]) and three novel de novo QRICH1 variants, respectively. These included two frameshift mutations (c.832_833del; p. [semanticscholar.org]

De novo loss-of-function variants in QRICH1 were subsequently identified in three patients presenting with developmental delay/intellectual disability in Ververi et al., 2017; one of these three patients was also diagnosed with ASD. [gene.sfari.org]

Ververi Brady Syndrome is a de novo mutation in the QRICH1 gene that presents with intellectual disability, hypertonia, dysphagia and mild dysmorphism. This Syndrome is not progressive unlike her other one. [rarediseaseday.org]

• Developmental Disorder

  disorder, and loss‐of‐function variants in QRICH1 were implicated in its etiology. [semanticscholar.org]

  disorder, and loss-of-function variants in QRICH1 were implicated in its aetiology. [physiciansweekly.com]

  […] shape; Pyloric stenosis; Metopic synostosis; Attention deficit hyperactivity disorder; Hypotonia 1 0 0 1 Growth delay due to insulin-like growth factor I resistance 1 0 0 1 Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities [clinvarminer.genetics.utah.edu]

  Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No - 3 Recent Recommendation Phenotypic spectrum associated with de novo mutations in QRICH1 gene Ververi A, et al. (2017) No ASD 4 Support De Novo Sequence and [gene.sfari.org]

  ORPHA:860 Intellectual Developmental Disorder With Cardiac Defects And Dysmorphic Facies Tetralogy of Fallot, Patent foramen ovale, Patent ductus arteriosus, Atrial septal defect, Double... [mousephenotype.org]

• Congestive Heart Failure

  ORPHA:230 Aneurysm Of Sinus Of Valsalva Oliguria, Aortic regurgitation, Congestive heart failure, Bacterial endocarditis, Heart murmur, D... [mousephenotype.org]

• Tachypnea

  These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen [ncbi.nlm.nih.gov]

• Respiratory Distress

  Perinatal period complicated with respiratory distress, low birth weight, cleft palate and hypospadias. During infancy, he was diagnosed with bilateral congenital cataracts and cryptorchidism. [gimjournal.org]

• Heart Disease

  Transposition of the great arteries MedGen UID: 21245 •Concept ID: C0040761 • Congenital Abnormality Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. [ncbi.nlm.nih.gov]

  OMIM:266920 Kallmann Syndrome-Heart Disease Syndrome Renal agenesis, Dilated cardiomyopathy, Aortic regurgitation, Pulmonary artery hypoplasia, Pulmon... [mousephenotype.org]

• Heart Murmur

  These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen [ncbi.nlm.nih.gov]

  ORPHA:230 Aneurysm Of Sinus Of Valsalva Oliguria, Aortic regurgitation, Congestive heart failure, Bacterial endocarditis, Heart murmur, D... [mousephenotype.org]

• Heart Failure

  Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death. [ncbi.nlm.nih.gov]

  ORPHA:230 Aneurysm Of Sinus Of Valsalva Oliguria, Aortic regurgitation, Congestive heart failure, Bacterial endocarditis, Heart murmur, D... [mousephenotype.org]

• Hypotension

  These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen [ncbi.nlm.nih.gov]

  ORPHA:906 Cocaine Intoxication Intestinal perforation, Nausea, Hypertension, Prolonged QRS complex, Bloody diarrhea, Hypotension... [mousephenotype.org]

• Cyanosis

  […] can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis [ncbi.nlm.nih.gov]

• Blepharitis

  ORPHA:572 Pyoderma Gangrenosum Myositis, Inflammation of the large intestine, Rheumatoid arthritis, Pustule, Myeloid leukemia ORPHA:48104 Wiskott-Aldrich Syndrome Microcytic anemia, Blepharitis, Anemia, Hematemesis, Otitis media, Abnormal platelet morphology [mousephenotype.org]

• Low Set Ears

  […] malformation Cupped ear Low-set ears Macrotia Growth abnormality Fetal growth restriction Short stature IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate [ncbi.nlm.nih.gov]

• Macrotia

  […] irregularity Microcephaly Scoliosis Abnormality of the nervous system Autistic behavior Delayed speech and language development Hyporeflexia Intellectual disability Intention tremor Motor delay Unsteady gait Ear malformation Cupped ear Low-set ears Macrotia [ncbi.nlm.nih.gov]

• Muscle Weakness

  Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Scoliosis MedGen UID: 11348 •Concept ID: C0036439 • Disease or Syndrome The presence of an abnormal lateral curvature of the spine. [ncbi.nlm.nih.gov]

• Bulbous Nose

  [from OMIM] Show allHide all Abnormality of head or neck Broad nasal tip Bulbous nose Everted lower lip vermilion High palate Prominent nose Smooth philtrum Thin upper lip vermilion Upslanted palpebral fissure Wide mouth Wide nose Abnormality of limbs [ncbi.nlm.nih.gov]

• Suggestibility

  In vitro studies showed that the R536X variant resulted in decreased protein expression, suggesting haploinsufficiency. [findzebra.com]

  It has been suggested that mutations in QRICH1 cause VERBRAS. [genome.jp]

  Enlargement of the cohort by these four individuals contributes to the delineation of the VBS phenotype and suggests expressive speech delay, moderate motor delay, learning difficulties/ mild ID, mild microcephaly, short stature and notable social behavior [physiciansweekly.com]

  It has been suggested that mutations in QRICH1 cause VERBRAS. Congenital malformation QRICH1 [HSA:54870] [KO:K24297] [kegg.jp]

  A CT scan revealed suggestive findings of dysmorphic cortical ribbon in the sylvian, peri-sylvian and frontal regions. Exome sequencing revealed a heterozygous variant in QRICH1 (NM_001320580.1):c.1672-1G>A (r.spl), classified as likely pathogenic. [gimjournal.org]

• Cryptorchidism

  During infancy, he was diagnosed with bilateral congenital cataracts and cryptorchidism. Additional medical features included short stature and postnatal microcephaly. He underwent numerous surgeries for his congenital cataracts. [gimjournal.org]

• Tremor

  0002080 HP:0002080 Intention tremor 0 AKT1 CL E G H 207 615109 Cowden syndrome 6 615109 C3554519 OMIM 1 380 391 164730 HP:0002080 HP:0002080 Intention tremor 0 ATCAY CL E G H 85300 94122 ORPHA 1 179 779 608179 HP:0002080 HP:0002080 Intention tremor 0 [mseqdr.org]

  Intention tremor MedGen UID: 1642960 •Concept ID: C4551520 • Sign or Symptom A type of kinetic tremor that occurs during target directed movement is called intention tremor. [ncbi.nlm.nih.gov]

  She had an unsteady gait, leg pain after walking, frequent falls, intention tremor, decreased muscle tone and reflexes, and involuntary tongue movements. Dysmorphic features included ptosis and hypertelorism. [findzebra.com]

• Delayed Speech and Language Development

  […] skeletal maturation Hypotonia Metaphyseal irregularity Microcephaly Scoliosis Abnormality of the nervous system Autistic behavior Delayed speech and language development Hyporeflexia Intellectual disability Intention tremor Motor delay Unsteady gait [ncbi.nlm.nih.gov]

• Hyporeflexia

  […] the eye Hypertelorism Ptosis Abnormality of the musculoskeletal system Delayed skeletal maturation Hypotonia Metaphyseal irregularity Microcephaly Scoliosis Abnormality of the nervous system Autistic behavior Delayed speech and language development Hyporeflexia [ncbi.nlm.nih.gov]

In the hope treatment will eventually become available, Phoebe and Joe are trying to raise funds for it. The youngster started to have trouble eating and walking. [nypost.com]

Hoping that a treatment will eventually become available, Phoebe and Joe try to raise funds for it. The boy had trouble eating and walking. [ustimetoday.com]

Since Florence is not expected to live into teens and gene therapy is the only treatment, the family has set up a GoFundMe page to help study this condition. Pheobe said: “We are saving all the penny for potential treatments and techniques. [exbulletin.com]

Her parents – who say she has “the most infectious belly laugh” – are fighting to give her the best life possible by raising £100,000 in the hope of getting pioneering treatment. [mirror.co.uk]

However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.\n\nSome people with treated CCHD have few related health problems later in life. [ncbi.nlm.nih.gov]

Phoebe and her husband, Joe, are desperately hoping that gene therapy will become available to improve their daughter’s prognosis, but the treatment is only in the research phases in the US as clinical trials have yet to be approved by the Food and Drug [nypost.com]

Phoebe and Joe desperately hope that gene therapy will become available to improve their daughter’s prognosis, but the treatment is still in the research stage in the United States, pending approval of clinical trials by the Food and Drug Administration [ustimetoday.com]

Phoebe and Joe are keen to have gene therapy available to improve their daughter’s prognosis, but treatment is in the United States because clinical trials have not yet been approved by the Food and Drug Administration (FDA). [exbulletin.com]

[…] and Dagmar Wieczorek and Silke Redler}, journal={Clinical Genetics}, year={2020}, volume={99}, pages={199 - 207} } Ververi‐Brady syndrome (VBS, # 617982) is a rare developmental disorder, and loss‐of‐function variants in QRICH1 were implicated in its etiology [semanticscholar.org]

CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. [ncbi.nlm.nih.gov]