Renpenning Syndrome

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Nora Tang	+ 597 word(s)	597	2020-12-15 07:36:55

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/renpenning-syndrome

Renpenning syndrome is a disorder that almost exclusively affects males, causing developmental delay, moderate to severe intellectual disability, and distinctive physical features.

genetic conditions

1. Introduction

Individuals with Renpenning syndrome typically have short stature and a small head size (microcephaly). Facial features characteristic of this disorder include a long, narrow face; outside corners of the eyes that point upward (upslanting palpebral fissures); a long, bulbous nose with a low-hanging separation between the nostrils (overhanging columella); a shortened space between the nose and mouth (philtrum); and cup-shaped ears. Males with Renpenning syndrome generally have small testes. Seizures and wasting away (atrophy) of muscles used for movement (skeletal muscles) may also occur in this disorder.

About 20 percent of individuals with Renpenning syndrome also have other features, which may include a gap or split in structures that make up the eye (coloboma), an opening in the roof of the mouth (cleft palate), heart abnormalities, or malformations of the anus.

Certain combinations of the features that often occur in Renpenning syndrome are sometimes called by other names, such as Golabi-Ito-Hall syndrome or Sutherland-Haan syndrome. However, all these syndromes, which have the same genetic cause, are now generally grouped under the term Renpenning syndrome.

2. Frequency

Renpenning syndrome is a rare disorder; its prevalence is unknown. More than 60 affected individuals in at least 15 families have been identified.

3. Causes

Renpenning syndrome is caused by mutations in the PQBP1 gene. This gene provides instructions for making a protein called polyglutamine-binding protein 1. This protein attaches (binds) to stretches of multiple copies of a protein building block (amino acid) called glutamine in certain other proteins.

While the specific function of polyglutamine-binding protein 1 is not well understood, it is believed to play a role in processing and transporting RNA, a chemical cousin of DNA that serves as the genetic blueprint for the production of proteins.

In nerve cells (neurons) such as those in the brain, polyglutamine-binding protein 1 is found in structures called RNA granules. These granules allow the transport and storage of RNA within the cell. The RNA is held within the granules until the genetic information it carries is translated to produce proteins or until cellular signals or environmental factors trigger the RNA to be degraded. Through these mechanisms, polyglutamine-binding protein 1 is thought to help control the way genetic information is used (gene expression) in neurons. This control is important for normal brain development.

Most of the mutations in the PQBP1 gene that cause Renpenning syndrome result in an abnormally short polyglutamine-binding protein 1. The function of a shortened or otherwise abnormal protein is likely impaired and interferes with normal gene expression in neurons, resulting in abnormal development of the brain and the signs and symptoms of Renpenning syndrome.

4. Inheritance

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation typically has to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

5. Other Names for This Condition

Golabi-Ito-Hall syndrome
Hamel cerebropalatocardiac syndrome
Porteous syndrome
Sutherland-Haan syndrome
X-linked intellectual deficit due to PQBP1 mutations
X-linked intellectual deficit, Renpenning type

References

Cossée M, Demeer B, Blanchet P, Echenne B, Singh D, Hagens O, Antin M, FinckS, Vallee L, Dollfus H, Hegde S, Springell K, Thelma BK, Woods G, Kalscheuer V,Mandel JL. Exonic microdeletions in the X-linked PQBP1 gene in mentally retarded patients: a pathogenic mutation and in-frame deletions of uncertain effect. Eur JHum Genet. 2006 Apr;14(4):418-25.
Flynn M, Zou YS, Milunsky A. Whole gene duplication of the PQBP1 gene insyndrome resembling Renpenning. Am J Med Genet A. 2011 Jan;155A(1):141-4. doi:10.1002/ajmg.a.33756.
Germanaud D, Rossi M, Bussy G, Gérard D, Hertz-Pannier L, Blanchet P, Dollfus H, Giuliano F, Bennouna-Greene V, Sarda P, Sigaudy S, Curie A, Vincent MC,Touraine R, des Portes V. The Renpenning syndrome spectrum: new clinical insightssupported by 13 new PQBP1-mutated males. Clin Genet. 2011 Mar;79(3):225-35. doi: 10.1111/j.1399-0004.2010.01551.x.
Kleefstra T, Franken CE, Arens YH, Ramakers GJ, Yntema HG, Sistermans EA,Hulsmans CF, Nillesen WN, van Bokhoven H, de Vries BB, Hamel BC.Genotype-phenotype studies in three families with mutations in thepolyglutamine-binding protein 1 gene (PQBP1). Clin Genet. 2004 Oct;66(4):318-26.
Kunde SA, Musante L, Grimme A, Fischer U, Müller E, Wanker EE, Kalscheuer VM. The X-chromosome-linked intellectual disability protein PQBP1 is a component ofneuronal RNA granules and regulates the appearance of stress granules. Hum MolGenet. 2011 Dec 15;20(24):4916-31. doi: 10.1093/hmg/ddr430.
Lenski C, Abidi F, Meindl A, Gibson A, Platzer M, Frank Kooy R, Lubs HA,Stevenson RE, Ramser J, Schwartz CE. Novel truncating mutations in thepolyglutamine tract binding protein 1 gene (PQBP1) cause Renpenning syndrome and X-linked mental retardation in another family with microcephaly. Am J Hum Genet. 2004 Apr;74(4):777-80.
Lubs H, Abidi FE, Echeverri R, Holloway L, Meindl A, Stevenson RE, SchwartzCE. Golabi-Ito-Hall syndrome results from a missense mutation in the WW domain ofthe PQBP1 gene. J Med Genet. 2006 Jun;43(6):e30.
Martínez-Garay I, Tomás M, Oltra S, Ramser J, Moltó MD, Prieto F, Meindl A,Kutsche K, Martínez F. A two base pair deletion in the PQBP1 gene is associatedwith microphthalmia, microcephaly, and mental retardation. Eur J Hum Genet. 2007 Jan;15(1):29-34.
Musante L, Kunde SA, Sulistio TO, Fischer U, Grimme A, Frints SG, Schwartz CE,Martínez F, Romano C, Ropers HH, Kalscheuer VM. Common pathological mutations in PQBP1 induce nonsense-mediated mRNA decay and enhance exclusion of the mutantexon. Hum Mutat. 2010 Jan;31(1):90-8. doi: 10.1002/humu.21146.
Stevenson RE, Bennett CW, Abidi F, Kleefstra T, Porteous M, Simensen RJ, Lubs HA, Hamel BC, Schwartz CE. Renpenning syndrome comes into focus. Am J Med GenetA. 2005 May 1;134(4):415-21.
Tapia VE, Nicolaescu E, McDonald CB, Musi V, Oka T, Inayoshi Y, Satteson AC,Mazack V, Humbert J, Gaffney CJ, Beullens M, Schwartz CE, Landgraf C, Volkmer R, Pastore A, Farooq A, Bollen M, Sudol M. Y65C missense mutation in the WW domainof the Golabi-Ito-Hall syndrome protein PQBP1 affects its binding activity andderegulates pre-mRNA splicing. J Biol Chem. 2010 Jun 18;285(25):19391-401. doi:10.1074/jbc.M109.084525.

©Text is available under the terms and conditions of the Creative Commons-Attribution ShareAlike (CC BY-SA) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Genetics & Heredity

Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Nora Tang

View Times: 442

Entry Collection: MedlinePlus

Update Date: 24 Dec 2020

Table of Contents

Video Upload Options

Confirm

1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

Video Upload Options

Confirm

1. Introduction

2. Frequency

3. Causes

3.1. The Gene Associated with Renpenning Syndrome

4. Inheritance

5. Other Names for This Condition

References