Each month CDO will select a few recently published genetic journal articles which we believe present the most interesting and important new findings with regard to rare chromosome disorders. Although the language contained in most journal articles may at times be technical and challenging, every effort has been made to present the following information in an easy to understand manner. Remember to visit this page monthly for new developments!

Further details on CDO’s library of information are available at www.chromodisorder.org/library.aspx In addition to on demand downloads, current members may request electronic information packets which include journal articles specifically chosen for their or their child’s chromosomal karyotype.

1q23q24 Deletions (CAKUT)

   The authors report 8 patients with deletions in 1q23.3q24.1 that all have been diagnosed with congenital anomalies of the kidney and urinary tract (CAKUT). 

  Full Abstract (English)         

1q43q44 Microdeletion

   The authors present a detailed characterization of individuals with microdeletions of 1q43q44 with the goal of identifying the genes that contribute to the different clinical features of this syndrome.

  Full Abstract (English)         

17p11.2

  The authors report on two distinct neurodevelopmental disorders that arise from chromosomal changes at 17p11.2: Potocki-Lupski syndrome (PTLS), which arises from a duplication, and Smith-Magenis syndrome (SMS), which arises from a deletion. 

  Full Abstract (English)         

Complete Ring Chromosome 4

  The authors report on a boy whose cytogenetic examination revealed a complete ring chromosome 4 without actual loss of genetic material. 

  Full Abstract (English)         

Deletion 11p13 (Aniridia and WAGR Syndrome)

   Both isolated aniridia and aniridia in the WAGR syndrome may be caused by deletions of the 11p13 chromosomal segment. The authors used customized targeted array-based CGH to study a group of Spanish patients with aniridia and related ocular abnormalities.

  Full Abstract (English)         

Deletion 11q (Jacobsen Syndrome)

   Jacobsen syndrome is caused by a deletion of chromosome 11q and characterized by congenital heart disease, intellectual disability, behavioral problems, Paris-Trousseau bleeding disorder, structural kidney defects and immunodeficiency. Patient studies and treatment conclusions are presented here.

  Full Abstract (English)         El Resumen (Español)

17q11.2 (NF1 Gene Mutations and Deletions)

   Neurofibromatosis type 1 is a tumor predisposition syndrome that in most cases is caused by mutations of the NF1 gene, located at 17q11.2.  Comparison of the clinical characteristics in patients with point mutations and deletions showed that patients with deletions are more severely affected. The different effects are described here.

  Full Abstract (English)         El Resumen (Español)

17q24.2 (PSMD12 Gene Mutations and Deletions)

   The protein PSMD12 plays an important role in nervous system development and function. The gene coding PSMD12 is located at 17q24.2. Studies of patients with both deletions and mutations of this gene was done, and the findings are described here. These studies suggest that PSMD12 is the primary factor that causes the features associated with deletion 17q24.2.

  Full Abstract (English)         El Resumen (Español)

3q22.3 mutations of STAG1

  The cohesin complex plays an important role in regulating chromosome segregation during cell division, gene expression and DNA repair. One of the cohesin complex genes, STAG1, is located on segment 3q22.3. The authors present 4 patients with small (<0.5 Mb) deletions of STAG1 and the PCCB gene, 3 with intragenic deletions of STAG1 and 10 with point mutations in the STAG1 gene. 

  Full Abstract (English)         

7q36.3 Microduplication (SHH long-range regulator)

   The Sonic hedgehog (shh) gene is required for normal development of the limbs and digits (fingers and toes). Here, the authors describe the case of a 1-year-old female with TPT-PS as well as the congenital heart disease, Tetralogy of Fallot. 

  Full Abstract (English)         

Chromosome 9 Duplication

  Variations in chromosome 9 are commonly found in the normal population and are not associated with disease features. Heterochromatic variations are changes in the heterochromatin, the densely packed DNA that is not being actively transcribed. Inversions near the centromere are also common on chromosome 9, and these regions also do not usually result in disease features because they do not contain any genes. Here, the authors present a case report of a female child that was first examined at 32 months of age who presented with neurodevelopmental delays and dysmorphic facial features

  Full Abstract (English)        

1p36.11 Microduplication (ARID1A Gene)

   ARID1A mutations can also occur during embryonic development resulting in the mutation being expressed in every cell. Loss of ARID1A has been shown to cause defective development of the nervous system. In this article, the authors characterize four patients with microduplications of chromosome 1p36.11, the region containing the ARID1A gene, and suggest that duplications of ARID1A can also cause a human syndrome. 

  Full Abstract (English)         El Resumen (Español)

12q Duplication

  Inverse Marcus Gunn phenomenon (also known as congenital facial synkinesis) results in an involuntary eye drooping (ptosis) when the jaw is moving. Here, they present a case report of a boy who was examined at 19 months of age. Chromosome analysis revealed an unbalanced translocation resulting in a duplication of part of chromosome 12 (12q24.1-q24.33), and a small deletion of chromosome 1 (1p36.33). There has been one other reported case of classic Marcus Gunn occurring in a patient with a duplication of chromosome 12q24.1-24.2. The authors suggest that his region likely contains the genes that can cause facial synkinesis.

  Full Abstract (English)         El Resumen (Español)

17p13.3 Microdeletion

  Deletions of chromosome 17p13.3 are associated with severe brain abnormalities due to the deletion of the gene PAFAB1H1. Here, they present a case report of a 3-year old boy with a 2.1 Mb microdeletion of 17p13.3 that deletes 42 genes. The authors compare the features of this patient with previously reported cases to determine the genes that are responsible for certain features. 

  Full Abstract (English)        El Resumen (Español)

Chromosome 2q32q33 (SATB2–Associated Syndrome)

  In this article, the authors present a review of SATB2-associated syndrome (SAS) and provide recommendations for future studies and treatment plans.

  Full Abstract (English)        El Resumen (Español)

Partial Trisomy 6p22.3-pter

  Partial trisomy of chromosome 6 results in a characteristic set of features. Individuals with this trisomy often present with low birth weight, developmental delay, growth retardation, craniofacial abnormalities, feeding difficulties, frequent respiratory infections and heart and kidney problems. Here, they present a case report of a 2-year old boy with a very rare "pure" trisomy of chromosome 6.  

  Full Abstract (English)         El Resumen (Español)

 17q12 Deletion

  Deletions of 17q12 are frequently associated with kidney problems and neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). A study of 7 fetuses with hyperechogenic kidneys was performed. A prenatal finding of hyperechogenic kidneys and detection of the 17q12 deletion are highly correlated with neurodevelopmental disorders including ASD.

  Full Abstract (English)         El Resumen (Español)

Duplication 3q and de novo Duplication 3q26.32-q27.2

  The authors provide a review of what is known about pure duplications of chromosome 3q, and report a patient with a duplication of 3q and a clinical diagnosis of Currarino syndrome (CS). CS is known to result from mutations in the MNX1 gene, however, sequencing analysis revealed that this patient did not have a mutation in this gene. Instead, he had a 7.9 Mb duplication of chromosome 3q26.32-q27.2. The authors present information regarding the genes found in the duplicated region that could cause the observed features. This review suggests that patients that present with CS but do not have MNX1 mutations should have chromosome screening done to see if there may be a duplication of 3q.

  Full Abstract (English)        El Resumen (Español)

Deletion 7p15.2 (Deletion of the HOXA13 gene)

  Hand-Foot-Genital Syndrome (HFGS) is a rare disease cause by mutations in the HOXA13 gene. Here, the authors report a young male child with a small deletion of 7p15.2 that removes HOXA13 gene.

  Full Abstract (English)        El Resumen (Español)

Deletion 19q12-q13.11 (TSHZ3 deletion)

  Autism Spectrum Disorder (ASD) is known to have genetic causes, and new genes that result in ASD characteristics are still being discovered. Here, the authors identify seven new patients from six families that have neurodevelopmental defects resulting from deletions in 19q12-q13.11, which includes the gene, TSHZ3. Studies indicate that TSHZ3 is a new gene linked to ASD and it is required for the normal development of the cortical projection neurons in the neocortex.

  Full Abstract (English)        El Resumen (Español)

Duplicaton of 7q11.23

  Duplications of 7q11.23 result in a syndrome characterized by autism, intellectual disability, speech and language delays, social anxiety and behavioral problems. Other characteristics include craniofacial, brain, and cardiac abnormalities. Here, the authors present a case study of a family where 5 members (father, 3 daughters, 1 son) carry duplications in 7q11.23. The most interesting finding from this paper is how different the clinical features are in each of these family members, even though they all have the exact same mutation.

  Full Abstract (English)        El Resumen (Español)

11q Terminal Deletion (Jacobson Syndrome)

  Jacobsen syndrome (JS) results from a terminal deletion of chromosome 11q and affects many organ systems. It has also been reported that JS patients also suffer from recurring infections due to deficits in the immune system. Here, the authors present a case report of a 16-year old female who presented with chronic viral and bacterial infections at the age of 12, along with typical JS symptoms.

  
  Full Abstract (English)       El Resumen (Español)

15q11.2 BP1-BP2 Microdeletions and Microduplications

  Many neurodevelopmental diseases result from changes in the number of copies of a specific genetic sequence, also known as copy number variations (CNVs). One chromosomal region where changes in CNVs occur frequently is 15q11.2 BP1-BP2. This region includes four genes, TUBGCP5, CYFIP1, NIPA2, and NIPA1. Here, the authors screened 294 families with neurodevelopmental disorders and identified 6 patients/families with either duplications or deletions of chromosome 15q11.2. 

  Full Abstract (English)        El Resumen (Español)

Deletion of 1p13.2

  This article describes an individual that has many symptoms characteristic of Noonan Syndrome. However, this patient, however, did not carry a mutation in any of the known genes linked to Noonan Syndrome. The patient, and nine additional cases, had a microdeletion of chromosome 1p13.2. All of them present with features characteristic of Noonan Syndrome, and the deletion includes the NRAS gene. Therefore, the authors suggest that the Noonan Syndrome features exhibited by individuals with microdeletions of 1p13.2 likely result from loss of the NRAS gene. 

  Full Abstract (English)       El Resumen (Español)

Microdeletion 1q41q42 (ASPP2 deficiency)

  Microdeletions of chromosome 1q41q42 result in characteristic facial features, intellectual disability and brain morphology defects. In this article, the authors identified 26 individuals with the 1q41q42 microdeletion that have undergone brain imaging. Of these, 19 had structural brain abnormalities, and they all were missing three genes, CAPN2, TP53BP2 and CAPN8. TP53BP2 is the most highly expressed in the brain. TP53BP2 encodes the protein ASPP2 and is required for normal development. Test results suggest that TP53BP2 may cause many of the characteristics associated with this syndrome. 

  
  Full Abstract (English)       El Resumen (Español)

Smith-Magenis Syndrome

  The Social Security Administration (SSA) has a program, the Compassionate Allowances List (CAL), that allows for the quicker receipt of disability benefits without the traditional application process. This review examines if Smith-Magenis Syndrome (SMS) qualifies to be included on the CAL. 


  Full Abstract (English)       El Resumen (Español)

Duplication of 2q24.3

  Duplications in 2q24.3 are associated with early onset infantile seizures. Here, the authors describe eight new cases of 2q24.3 duplication from four different families. With the exception of one patient, all of the other cases presented here suggest that duplication of the gene SCN2A results in seizures that appear within the first few days after birth. There seems to be some variability in the level of intellectual and developmental disabilities ranging from no disability to severe. This suggests that SCN2A duplication itself cannot cause intellectual and developmental delays and they likely result from changes in other genetic factors.

  Full Abstract (English)       El Resumen (Español)

4p16.3 - Wolf­Hirschhorn syndrome (WHS)

  Deletions in chromosome 4p16.3 lead to Wolf­Hirschhorn syndrome (WHS), a disease characterized by growth delay, seizures, intellectual disability and distinct facial features.  The authors use this data to refine the critical region that leads to the features of WHS. They were able to further characterize the chromosomal abnormalities associated with WHS, narrow down the region that causes seizures, and identify a new disease­-causing region in patients with microduplications of 4p16.3. 

  Full Abstract (English)       El Resumen (Español)

Duplication of 16p11.2

  The 16p11.2 duplication is often associated with Autism Spectrum Disorder (ASD); however, the severity of associated features can be quite variable. Here, the authors assess people that have the 16p11.2 duplication for various intellectual and behavioral features. Their results were compared to family members who did not carry this duplication. Even though there is an elevated risk of autism, there are many patients who do not develop autism traits and many individuals fall within the normal ranges for many features. It is likely there are additional “modifiers” that may influence the severity of autism including additional genetic factors. 

  Full Abstract (English)       El Resumen (Español)

Duplication of 15q11.2­q13.1

  Duplication of 15q11.2­q13.1 (Dup 15q syndrome) is one of the more common genetic causes of autism spectrum disorder (ASD). Here, the authors compare children with Dup 15q syndrome to those with non­syndromic ASD and identify developmental and behavioral features that are specifically associated with Dup 15q syndrome. The findings suggest that there is a strong correlation between language, non­verbal communication and daily living skills in the Dup15q group, and that early interventions should focus on treatment of the epilepsy and the development of language and motor skills

  Full Abstract (English)       El Resumen (Español)

Partial Trisomy 21

  The characteristic features of Down’s Syndrome (DS) are known to be caused by having three copies of chromosome 21 (instead of two). The authors discovered a very small region (34 kb on 21q22.13) that they called the highly restricted Down Syndrome Critical Region (HR-DSCR), and it was only found in the individuals with features of DS and not in those without the DS features. This region does not contain any known genes and the sequence is not well conserved with other animals.

  Full Abstract (English)       El Resumen (Español)       

Phelan-McDermid Syndrome (del 22q13.3)

  Phelan-McDermid syndrome (PMS), caused by the 22q13.3 deletion, is characterized by global developmental delay, cognitive deficits and autistic behavior. The authors perform a descriptive study on 34 children with the deletion, including the gene SHANK3, which is considered responsible for the neurodevelopmental features of PMS. All patients showed significant developmental delay. The data collected suggest that there is a maximal level of behavioral functioning in individuals with PMS and that, as these children age, there is some stagnation or even regression in further development. Four children with small deletions that included SHANK3 and two neighboring genes, RABL2B and ACR, had better motor and language characteristics. This may indicate that there is participation from other genes in the developmental phenotype of PMS patients. 

  Full Abstract (English)      El Resumen (Español) 

Pitt-Hopkins Syndrome

  Pitt-­Hopkins syndrome (PTHS) is a very rare disease, caused predominantly by mutations in TCF4, and is characterized by intellectual disability, abnormal breathing patterns and specific facial features including deep­set eyes, a broad nasal base, and a wide mouth with tented upper lip. The authors have developed a secure web­based system, waihonopedia, that will allow for the collection of data from patients. As of this study, there were 101 individuals that completed the questionnaire, and common traits have been outlined. Waihonopedia will allow for the follow­up of patients over time and provide additional data characterizing the natural course of a disease and, hopefully, lead to better diagnostic methods.

  Full Abstract (English)       El Resumen (Español)

2p15p16.1 Microdeletion Syndrome

  The 2p15p16 deletion syndrome is characterized by features that include: intellectual disability, microcephaly, hypotonia, delayed growth, common craniofacial features, and digital anomalies. Examination of the twenty available cases revealed that there are four genes (XPO1, USP34, BCL11A, and REL) that are most frequently affected and were shown to be very strong candidate genes for the 2p15p16.1 microdeletion syndrome.

  Full Abstract (English)       El Resumen (Español)

Williams-Beuren syndrome (Microdeletion 7q11.23)

  Williams-Beuren syndrome (WBS) results from a hemizygous microdeletion of chromosome 7q11.23. WBS is characterized by cognitive impairment, dysmorphic facial features, supravalvular aortic stenosis, and, in many cases, endocrine dysfunction Here, they summarize their findings characterizing features and outcomes related to endocrine dysfunction. A significant number of patients present with endocrine problems that vary in the levels of severity. With treatment they can be managed with long-term follow-up.

  Full Abstract (English)       El Resumen (Español)

Monosomy 1p36

  This study was done to see if there is a link between the size of 1p36 deletions and the characteristics shown by patients.  This group concluded that there is no correlation between deletion size and severity of the syndrome; the largest deletions do not necessarily lead to the most severe clinical features. 

  Full Abstract (English)       El Resumen (Español)

Deletion 5q14.3-5q15 (Bosch-Boonstra-Schaaf Syndrome)

  Bosch-Boonstra-Schaaf syndrome is a complex of optic atrophy (deterioration of the optic nerve) and intellectual disability, caused by a loss-of-function in the NR2F1 gene, located at the boundary of 5q14.3 and 5q15. A study of twenty families generated a clinical picture of patients with this deletion.

  Full Abstract (English)        El Resumen (Español)

15q13.3 Microdeletion

  A full characterization of all traits associated with the microdeletion at 15q13.3 was done. This study revealed that there is a lot of variability in the behavioral and neurological deficits of patients with del 15q13.3 and future work will focus on identifying the genes that contribute to each trait. 
 

   Full Abstract (English)        El Resumen (Español)

Deletion 2p23

  Tatton-Brown-Rahman syndrome considered to be caused by mutations of the DNMT3A gene, located at 2p23. Okamoto et al. showed that deletion of this area may produce the same phenotype.

  Full Abstract (English)        El Resumen (Español)

Duplication 15q26.3

  Traditionally, we considered duplication of the 1GF1R gene as a cause of overgrowth in patients with distal duplications 15q. However, these authors showed that there are some other factors participating in this process.

  Full Abstract (English)       El Resumen (Español)

Deletion 3q29

  Creating a registry for 3q29 deletion syndrome creates a more objective image of its different traits.

  Full abstract (English)        Resumen (Español)

Deletion 6q16.1

  Two genes in this region are responsible for all characteristics of the 6q16.1 disorder.

  Full abstract (English)        Resumen (Español)

Duplication 12p11

  Research on the gene Parathyroid hormone-like hormone (PTHLH) has shown that it has an important role in bone formation. The major finding from this study is that only the duplication of PTHLH causes the specific form of skeletal dysplasia characterized by a short humerus, curved radius and brachydacyly, that is observed in this family.

  Full abstract (English)        Resumen (Español)

Deletion 2p25 

   To determine if SOX11 has a role in human nervous system development, existing databases were used to identify individuals with 2p25.2 deletions that include SOX11, as well as individuals with de novo mutations in SOX11. Case findings, experiments performed on frog embryos, and examination of SOX11 expression during human brain development suggest that SOX11 does indeed have an important role in nervous system development.

   Full abstract (English)        Resumen (Español)

5p deletion

   Deletion of the short arm of chromosome 5 is one of the most common deletion syndromes. Close to 90% of 5p deletions are de novo in origin. However, there are a few instances of familial inheritance. The authors describe families in which deletions are passed down from parent to child. The data from these families has helped to assign specific genes to specific traits. An interesting finding suggests that other genetic and perhaps environmental factors may contribute to the clinical features observed.

      Full abstract (English)        Resumen (Español)

6p22.3 

   The author tried to determine what gene or genes cause mesomelic dysplasias, which are skeletal disorders that result in a shortened segment in the middle limb. In three patients with a deletion of 6p22.3, four genes were deleted: MBOAT1, E2F3, CDKAL1, and SOX4; none are predicted to cause the skeletal problems observed. Another patient missing one additional gene, ID4 has no skeletal problems, meaning mesmeric dysplasia caused by the microdeletion at 6p22.3 may result from changes in the “regulatory regions” of the neighboring genes. The authors propose that the deletion of 6p22.3 causes these regions to be moved allowing them to activate the wrong genes at the wrong time.

   Full abstract (English)        Resumen (Español)

Smith-Magenis Syndrome 

   Smith-Magenis Syndrome (SMS) is characterized by sleep disturbances, craniofacial and skeletal anomalies, psychiatric behaviors (self-injury), metabolic problems and obesity. Typical SMS patients carry a microdeletion in 17p11.2 that deletes ~76 genes including the gene retinoic acid induced 1 (RAI1). RAI1 seems to be the primary gene causing the features associated with SMS. 

   Full abstract (English)        Resumen (Español)

17q21.31 

   Comparison of 27 patients with 17q21.31 deletion (which includes loss of the KASNL1 gene) and several patients with the KASNL1 loss of function mutations indicate that KASNL1 is the primary gene responsible for the 17q21.31 deletion syndrome.

   Full abstract (English)        Resumen (Español)

Review of 18p deletions 

   This article provides an overview of the current knowledge regarding 18p- deletions.  The authors have been able to identify the critical region for the following features: sensorineural hearing loss, ptosis, scoliosis/kyphosis, tetralogy of Fallot, seizures, sacral agenesis, white matter abnormalities, kidney abnormalities, pectus excavatum, structural pituitary anomalies, autoimmune conditions, congenital cataracts and congenital hip dysplasia.

   Full abstract (English)        Resumen (Español)

21q22.13

    In this article, the authors identify 14 people with mutations in the DYRK1A gene; five have microdeletions (21q22.12q22.3), three have small insertions or deletions (INDELs), and six have single DNA nucleotide changes (SNVs). The authors suggest that since most patients have the same characteristics it is likely that changes in the DYRK1A gene are responsible for the features of the 21q22.12q22.3 micro-deletion.

   Full abstract (English)        Resumen (Español)

1q21.1 copy-number variant 

   Behavioral, neurological and medical features of individuals that carry either a deletion or a duplication of the 1q21.1 region were characterized in this article.

   Full abstract (English)        Resumen (Español)

Duplication 8p23.1 

   In this article they examine four patients and five families representing eight microduplications of 8p23.1. The authors identify a “minimal region of overlap” (MRO) in the middle of 8p23.1 that causes the features associated with the duplication syndrome. The MRO contains 8 of the core 32 duplication syndrome genes including SOX7. The authors examined how the location of the duplication on the chromosome can affect the clinical features of the syndrome.

   Full abstract (English)        Resumen (Español)

Duplication 8p23.1 (2012)

   This is a follow-up paper that identified 6 additional patients with the 8p23.1 duplication. The authors examined five postnatal probands and one prenatal patient. The authors are trying to determine the genes that, when duplicated, result in the common features, including congenital heart defects. Two genes previously shown to be involved in heart development, GATA4 and SOX7, are found in the duplicated region and both are dosage sensitive, meaning that altered levels of protein can lead to variable changes in development. The authors suggest the variable expression of GATA4 and SOX7 in individuals with 8p23.1 duplication may lead to the variability of heart defects observed in patients with the syndrome.

   Full abstract (English)        Resumen (Español)