2p15-16.1 microdeletion is an extremely rare

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

caused by a small deletion in the short arm of human

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost e ...

. First described in two patients in 2007, by 2013 only 21 people have been reported as having the disorder in the

medical literature Medical literature is the scientific literature of medicine: articles in journals and texts in books devoted to the field of medicine. Many references to the medical literature include the health care literature generally, including that of denti ...

Presentation

As of 2013, only 21 patients with a 2p15-16.1 microdeletion had been identified. The clinical similarities between the individuals resulted in the classification of a new genetic

syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...

. The shared clinical features include moderate to severe

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...

and similar facial features including

telecanthus Telecanthus, or dystopia canthorum, refers to increased distance between the inner corners of the eyelids (medial canthi), while the inter-pupillary distance is normal. This is in contrast to hypertelorism, in which the distance between the w ...

, drooping eyelids, downslanting, short

palpebral fissure The palpebral fissure is the elliptic space between the medial and lateral canthi of the two open eyelids. In simple terms, it is the opening between the eyelids. In adult humans, this measures about 10 mm vertically and 30 mm horizontally. Va ...

s, a prominent

nasal bridge The nasal bridge is the upper, bony part of the human nose, which overlies the nasal bones. Association with epicanthic folds Low-rooted nasal bridges are closely associated with epicanthic folds. A lower nasal bridge is more likely to cause an ...

, high palate with long, smooth

philtrum The philtrum ( la, philtrum from Ancient Greek ''phíltron,'' lit. "love charm"), or medial cleft, is a vertical indentation in the middle area of the upper lip, common to therian mammals, extending in humans from the nasal septum to the tuberc ...

and an everted lower lip. Some of the patients also had feeding problems in infancy,

microcephaly Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...

optic nerve hypoplasia Optic nerve hypoplasia (ONH) is a medical condition arising from the underdevelopment of the optic nerve(s). This condition is the most common congenital optic nerve anomaly. The optic disc appears abnormally small, because not all the optic nerve ...

and

hydronephrosis Hydronephrosis describes hydrostatic dilation of the renal pelvis and calyces as a result of obstruction to urine flow downstream. Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dilation of t ...

, wide-spaced nipples, short stature, cortical dysplasia, camptodactyly and

pigeon toe Columbidae () is a bird family consisting of doves and pigeons. It is the only family in the order Columbiformes. These are stout-bodied birds with short necks and short slender bills that in some species feature fleshy ceres. They primarily ...

Cause

Three of the patients reported had a consistent

proximal Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position ...

breakpoint on chromosome 2, but varying

distal Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...

breakpoints. The patients have 2p15–16.1 deletions of 5.7

megabases A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

(Mb), 4.5 Mb, 3.9 Mb, 3.35Mb 3.3Mb and 570

kilobase A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DN ...

s, respectively. In all 21 patients the deletions are '' de novo'' — neither parent possessed nor transmitted the mutation to the affected individual. One patient is a

genetic mosaic Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilize ...

, having some cells with the deletion and others without.

Affected genes

The largest deletion encompasses approximately 15 protein-coding

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s, 6

pseudogene Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes ar ...

s and a number of other as yet uncharacterised candidates, including: *

AHSA2 AHSA2 also known as AHA1, activator of heat shock 90kDa protein ATPase homolog 2 (yeast) is a human gene which encodes a protein which acts as co-chaperone of Hsp90 (heat shock protein 90). AHSA2 and the related AHSA1 Activator of 90 kDa heat ...

, activator of heat shock 90kDa protein ATPase homolog *

BCL11A B-cell lymphoma/leukemia 11A is a protein that in humans is encoded by the ''BCL11A'' gene. Function The ''BCL11A'' gene encodes for a regulatory C2H2 type zinc-finger protein, that can bind to the DNA. Five alternatively spliced transcript ...

, B-cell lymphoma/leukemia 11A * C2orf74, Uncharacterized protein C2orf74 *

FANCL E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the ''FANCL'' gene. Function The clinical phenotype of mutational defects in all Fanconi anemia (FA) complementation groups is similar. This phenotype is characteriz ...

, E3 ubiquitin-protein ligase FANCL *

KIAA1841 KIAA1841 is a gene in humans that encodes a protein known as KIAA1841 (uncharacterized protein KIAA1841). KIAA1841 is targeted for the nucleus and it predicted to play a role in regulating transcription. Gene Location KIAA1841 is locat ...

, Uncharacterized protein KIAA1841 * PAPOLG, Poly(A) polymerase gamma *

PEX13 Peroxisomal membrane protein PEX13 is a protein that in humans is encoded by the ''PEX13'' gene. It located on chromosome 2 next to KIAA1841 Interactions PEX13 has been shown to interact with PEX14, PEX5 and PEX19 Peroxisomal biogenesis f ...

, Peroxisomal membrane protein Peroxin-13 * PUS10, Pseudouridylate synthase 10 * REL, C-Rel proto-oncogene protein * SNORA70B, small nucleolar RNA, H/ACA box 70B * USP34, Ubiquitin carboxyl-terminal hydrolase 34 *

VRK2 Serine/threonine-protein kinase VRK2 is an enzyme that in humans is encoded by the ''VRK2'' gene. This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. This gene is widely expressed in human ...

, Serine/threonine-protein kinase VRK2 *

XPO1 Exportin 1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), is a eukaryotic protein that mediates the nuclear export of various proteins and RNAs. History XPO1 (CRM1) originally was identified in the fission yeast ''Schizosaccharom ...

, Exportin-1

Diagnosis

Treatment

References

External links

* *

Orphanet Orphanet is a knowledge base dedicated to rare diseases as well as corresponding diagnosis, orphan drugs, clinical trials and expert networks The website is managed by a network of academic establishments from 40 countries, led by Inserm. It c ...

entry fo
2p15-16.1 microdeletion syndrome
* {{Medicine Autosomal monosomies and deletions Genetic anomalies Syndromes with intellectual disability Syndromes with craniofacial abnormalities Syndromes with microcephaly Syndromes with short stature Syndromes affecting the kidneys Syndromes with dysmelia Chromosomal abnormalities