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X-linked recessive inheritance is a mode of
inheritance Inheritance is the practice of passing on private property Private property is a legal designation for the ownership of property by non-governmental legal entities. Private property is distinguishable from public property Public property i ...

inheritance
in which a
mutation In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechan ...
in a
gene In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mecha ...

gene
on the
X chromosome The X chromosome is one of the two sex-determining chromosome A chromosome is a long DNA molecule with part or all of the genome, genetic material of an organism. Most eukaryotic chromosomes include packaging proteins called histones whic ...

X chromosome
causes the
phenotype In genetics Genetics is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular inter ...

phenotype
to be always expressed in males (who are necessarily
homozygous Zygosity (the noun, zygote, is from the Greek zygotos "yoked," from zygon "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an or ...
for the gene mutation because they have one X and one
Y chromosome The Y chromosome is one of two sex chromosome A chromosome is a long DNA molecule with part or all of the genome, genetic material of an organism. Most eukaryotic chromosomes include packaging proteins called histones which, aided by Chaper ...
) and in females who are homozygous for the gene mutation, see
zygosity Zygosity (the noun, zygote, is from the Greek zygotos "yoked," from zygon "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an org ...
. Females with one copy of the mutated gene are carriers. X-linked inheritance means that the gene causing the trait or the disorder is located on the X chromosome. Females have two X chromosomes while males have one X and one
Y chromosome The Y chromosome is one of two sex chromosome A chromosome is a long DNA molecule with part or all of the genome, genetic material of an organism. Most eukaryotic chromosomes include packaging proteins called histones which, aided by Chaper ...
. Carrier females who have only one copy of the mutation do not usually express the phenotype, although differences in
X-chromosome inactivation and calico cats is a visible manifestation of X-inactivation. The black and orange alleles of a fur coloration gene reside on the X chromosome. For any given patch of fur, the inactivation of an X chromosome that carries one allele results in th ...
(known as
skewed X-inactivation Skewed X-chromosome inactivation (skewed X-inactivation) occurs when the X-inactivation and calico cats is a visible manifestation of X-inactivation. The black and orange alleles of a fur coloration gene reside on the X chromosome. For any give ...
) can lead to varying degrees of clinical expression in carrier females, since some cells will express one X
allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is one of two, or more, forms of a given gene In biology, a gene (from ''genos'' "...Wilhelm Johannsen coined the word gene to describe the Mendelian_inheritance ...
and some will express the other. The current estimate of sequenced X-linked genes is 499, and the total, including vaguely defined traits, is 983.


Patterns of inheritance

In humans, inheritance of X-linked recessive traits follows a unique pattern made up of three points. * The first is that affected fathers cannot pass X-linked recessive traits to their sons because fathers give Y chromosomes to their sons. This means that males affected by an X-linked recessive disorder inherited the responsible X chromosome from their mothers. * Second, X-linked recessive traits are more commonly expressed in males than females. This is due to the fact that males possess only a single X chromosome, and therefore require only one mutated X in order to be affected. Women possess two X chromosomes, and thus must receive two of the mutated recessive X chromosomes (one from each parent). A popular example showing this pattern of inheritance is that of the descendants of Queen Victoria and the blood disease
hemophilia Haemophilia or hemophilia (from Greek language, Greek αίμα, ''hema'' 'blood', and φιλία, philia 'love of'), is a mostly hereditary, inherited genetic disorder that impairs the body's ability to coagulation, make blood clots, a proces ...
. * The last pattern seen is that X-linked recessive traits tend to skip generations, meaning that an affected grandfather will not have an affected son, but could have an affected grandson through his daughter. Explained further, all daughters of an affected man will obtain his mutated X, and will then be either carriers or affected themselves depending on the mother. The resulting sons will either have a 50% chance of being affected (mother is carrier), or 100% chance (mother is affected). It is because of these percentages that we see males more commonly affected than females.


Pushback on recessive/dominant terminology

A few scholars have suggested discontinuing the use of the terms ''dominant'' and ''recessive'' when referring to X-linked inheritance. The possession of two X chromosomes in females leads to dosage issues which are alleviated by
X-inactivation X-inactivation (also called Lyonization, after English geneticist Mary Lyon Mary Mason Lyon (; February 28, 1797 – March 5, 1849) was an American pioneer in women's education. She established the Wheaton College (Massachusetts), Wheaton ...
. Stating that the highly variable
penetrancePenetrance in genetics Genetics is a branch of biology concerned with the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) Though heredity had been observed for millennia, Gregor Mendel, Moravia, Moravian sc ...
of X-linked traits in females as a result of mechanisms such as skewed X-inactivation or
somatic mosaicismMosaicism or genetic mosaicism is condition in multi-cellular organism 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 fertilized egg. Gen ...
is difficult to reconcile with standard definitions of dominance and recessiveness, scholars have suggested referring to traits on the X chromosome simply as ''X-linked.''


Examples


Most common

The most common X-linked recessive disorders are:GP Notebook - X-linked recessive disorders
Retrieved on 5 Mars, 2009
* Red–green color blindness, a very common trait in humans and frequently used to explain X-linked disorders. Between seven and ten percent of men and 0.49% to 1% of women are affected. Its commonness may be explained by its relatively benign nature. It is also known as daltonism. *
Hemophilia A Haemophilia A (or hemophilia A) is a genetic deficiency in clotting factor VIII, which causes increased bleeding and usually affects males. In the majority of cases it is inherited as an X-linked recessive trait, though there are cases which arise ...
, a
blood clotting Coagulation, also known as clotting, is the process by which blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompressible In fluid mechanics or more generally continuum mech ...
disorder caused by a
mutation In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechan ...
of the
Factor VIII Factor VIII (FVIII) is an essential blood-clotting protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one l ...
gene In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mecha ...

gene
and leading to a deficiency of Factor VIII. It was once thought to be the "royal disease" found in the descendants of Queen Victoria. This is now known to have been Hemophilia B (see below). *
Hemophilia B Haemophilia B, also spelled Hemophilia B is a blood clotting Coagulation, also known as clotting, is the process by which blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompr ...
, also known as Christmas disease, a
blood clotting Coagulation, also known as clotting, is the process by which blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompressible In fluid mechanics or more generally continuum mech ...
disorder caused by a
mutation In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechan ...
of the
Factor IX Factor IX (or Christmas factor) () is one of the serine protease Serine proteases (or serine endopeptidases) are s that cleave s in s. serves as the at the (enzyme's) . They are found ubiquitously in both and . Serine proteases fall i ...

Factor IX
gene In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mecha ...

gene
and leading to a deficiency of Factor IX. It is rarer than
hemophilia A Haemophilia A (or hemophilia A) is a genetic deficiency in clotting factor VIII, which causes increased bleeding and usually affects males. In the majority of cases it is inherited as an X-linked recessive trait, though there are cases which arise ...
. As noted above, it was
common Common may refer to: Places * Common, a townland in County Tyrone County Tyrone (; ) is one of the thirty-two counties of Ireland Ireland (; ga, Éire ; Ulster Scots dialect, Ulster-Scots: ) is an island in the North Atlantic Ocean, ...
among the descendants of Queen Victoria. *
Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular disease A neuromuscular junction (or myoneural junction) is a ch ...
, which is associated with mutations in the
dystrophin Dystrophin is a rod-shaped cytoplasmic In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical s ...
gene. It is characterized by rapid progression of muscle degeneration, eventually leading to loss of skeletal muscle control, respiratory failure, and death. *
Becker's muscular dystrophy Becker muscular dystrophy is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and pelvis. It is a type of dystrophinopathy. This is caused by mutations in the dystrophin gene, which encodes t ...
, a milder form of Duchenne, which causes slowly progressive muscle weakness of the legs and
pelvis The pelvis (plural pelves or pelvises) is the lower part of the trunk, between the abdomen The abdomen (colloquially called the belly, tummy, midriff or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in ...

pelvis
. *
X-linked ichthyosis X-linked ichthyosis (abbreviated ''XLI'') is a skin condition caused by the genetic disorder, hereditary deficiency of the steroid sulfatase (STS) enzyme that affects 1 in 2000 to 1 in 6000 males. XLI manifests with dry, scaly skin and is due to ...
, a form of
ichthyosis Ichthyosis is a family of genetic skin disorder A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the Human body, body and includes skin, hair, ...
caused by a hereditary deficiency of the
steroid sulfatase Steroid sulfatase (STS), or steryl-sulfatase (), formerly known as arylsulfatase C, is a sulfatase Sulfatases are enzymes of the esterase class that catalyze the hydrolysis of sulfate esters. These may be found on a range of substrates, includi ...
(STS) enzyme. It is fairly rare, affecting one in 2,000 to one in 6,000 males. *
X-linked agammaglobulinemia X-linked agammaglobulinemia (XLA) is a rare genetic disorder discovered in 1952 that affects the body's ability to fight infection An infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, an ...
(XLA), which affects the body's ability to fight infection. XLA patients do not generate mature
B cell #REDIRECT B cell 3D rendering of a B cell B cells, also known as B lymphocytes, are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a ne ...
s. B cells are part of the immune system and normally manufacture antibodies (also called
immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystal ...

immunoglobulin
s) which defends the body from infections (the
humoral Humoral immunity is the aspect of immunity Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * Immunity (journal), ''Immunity'' (journal), a scientific journal published by Cell Press Biolo ...
response). Patients with untreated XLA are prone to develop serious and even fatal infections. *
Glucose-6-phosphate dehydrogenase deficiency Glucose-6-phosphate dehydrogenase deficiency (G6PDD) is an inborn error of metabolism Inborn errors of metabolism form a large class of genetic disease A genetic disorder is a health problem caused by one or more abnormalities in the genome. ...
, which causes nonimmune hemolytic anemia in response to a number of causes, most commonly infection or exposure to certain medications, chemicals, or foods. Commonly known as "favism", as it can be triggered by chemicals existing naturally in broad (or fava) beans.


Less common disorders

Theoretically, a mutation in any of the genes on chromosome X may cause disease, but below are some notable ones, with short description of symptoms: *
Adrenoleukodystrophy Adrenoleukodystrophy (ALD) is a genetic disorder, disease linked to the X chromosome. It is a result of fatty acid buildup caused by a defect in the very long chain of fatty acids transporter in peroxisomes, which then causes damage to the myelin ...

Adrenoleukodystrophy
; leads to progressive brain damage, failure of the adrenal glands and eventually death. *
Alport syndrome Alport syndrome is a genetic disorder affecting around 1 in 5,000-10,000 children, characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. Alport syndrome can also affect the eyes, though the changes do not usually affect s ...
; glomerulonephritis, endstage kidney disease, and hearing loss. A minority of Alport syndrome cases are due to an autosomal recessive mutation in the gene coding for
type IV collagen Collagen IV (ColIV or Col4) is a type of collagen found primarily in the basal lamina. The type IV collagen C4 domain, collagen IV C4 domain at the C-terminus is not removed in post-translational processing, and the fibers link head-to-head, rather ...
. *
Androgen insensitivity syndrome Androgen insensitivity syndrome (AIS) is an intersex condition with an estimated prevalence of about 1:20,000-64,000 in XY (chromosomally male) births, resulting in the partial or complete inability of the Animal cell, cell to respond to androgens. ...
; variable degrees of undervirilization and/or infertility in XY persons of either sex *
Barth syndrome Barth syndrome (BTHS) is an X-linked genetic disorder. The disorder, which affects multiple body systems, is diagnosed almost exclusively in males. It is named after Dutch pediatric neurologist Peter Barth. Presentation Though not always present, ...

Barth syndrome
; metabolism distortion, delayed motor skills, stamina deficiency, hypotonia, chronic fatigue, delayed growth, cardiomyopathy, and compromised immune system. *
Blue cone monochromacy Blue cone monochromacy (BCM) is an inherited eye disease This is a partial list of publishes a classification of known diseases and injuries, the International Statistical Classification of Diseases and Related Health Problems, or ICD-10. This li ...
; low vision acuity, color blindness, photophobia, infantile nystagmus. *
Centronuclear myopathy Centronuclear myopathies (CNM) are a group of congenital A birth defect, also known as a congenital disorder, is a condition present at birth Birth is the act or process of bearing or bringing forth offspring, also referred to in technical co ...
; where cell nuclei are abnormally located in skeletal muscle cells. In CNM the nuclei are located at a position in the center of the cell, instead of their normal location at the periphery. * Charcot–Marie–Tooth disease (CMTX2-3); disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms in the advanced stages of disease. *
Coffin–Lowry syndrome Coffin–Lowry syndrome is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome In the fields of molecular biology Molecular biology is the branch of biology Biology ...
; severe mental retardation sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis as well as auditory and visual abnormalities. *
Fabry disease Fabry disease, also known as Anderson–Fabry disease, is a rare genetic disease that can affect many parts of the body, including the kidneys, heart, and integumentary system, skin. Fabry disease is one of a group of conditions known as lysosoma ...
; A lysosomal storage disease causing anhidrosis, fatigue, angiokeratomas, burning extremity pain and ocular involvement. *
Hunter syndrome Hunter syndrome, or mucopolysaccharidosis Mucopolysaccharidoses are a group of metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients such as proteins, fats, and ...
; potentially causing hearing loss, thickening of the heart valves leading to a decline in cardiac function, obstructive airway disease, sleep apnea, and enlargement of the liver and spleen. *
Hypohidrotic ectodermal dysplasia Hypohidrotic ectodermal dysplasia is one of about 150 types of ectodermal dysplasia Ectodermal dysplasia (ED) is a group of genetic syndromes all deriving from abnormalities of the ectoderm The ectoderm is one of the three primary germ layer ...
, presenting with hypohidrosis, hypotrichosis, hypodontia *
Kabuki syndrome Kabuki syndrome (also previously known as Kabuki-makeup syndrome (KMS) or Niikawa–Kuroki syndrome) is a Birth defect, congenital disorder of Genetics, genetic origin. It affects multiple parts of the body, with varying symptoms and severity, alth ...

Kabuki syndrome
(the '' KDM6A'' variant); multiple congenital anomalies and mental retardation. *
Spinal and bulbar muscular atrophy Spinal and bulbar muscular atrophy (SBMA), popularly known as Kennedy's disease, is a progressive debilitating neurodegenerative disorder A neurodegenerative disease is caused by the progressive loss of structure or function of neuron A n ...
; muscle cramps and progressive weakness *
Lesch–Nyhan syndrome Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzy ...
; neurologic dysfunction, cognitive and behavioral disturbances including self-mutilation, and uric acid overproduction (hyperuricemia) * Lowe syndrome; hydrophthalmia, cataracts, intellectual disabilities, aminoaciduria, reduced renal ammonia production and vitamin D-resistant rickets *
Menkes disease Menkes disease (MNK), also known as Menkes syndrome, is an X-linked recessive X-linked recessive inheritance is a mode of inheritance Inheritance is the practice of passing on private property, Title (property), titles, debts, entitlements, ...
; sparse and coarse hair, growth failure, and deterioration of the nervous system * Nasodigitoacoustic syndrome; misshaped nose,
brachydactyly Brachydactyly (Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approxim ...

brachydactyly
of the
distal phalanges The phalanges (singular: ''phalanx'' ) are digital Digital usually refers to something using discrete digits, often binary digits. Technology and computing Hardware *Digital electronics Digital electronics is a field of electronics Th ...
, sensorineural deafness *
Nonsyndromic deafness Nonsyndromic deafness is hearing loss Hearing loss is a partial or total inability to hear Hearing, or auditory perception, is the ability to perceive Sound, sounds by detecting Vibration, vibrations, changes in the pressure of the su ...
; hearing loss *
Norrie disease Norrie disease is a rare disease A rare disease is any disease A disease is a particular abnormal condition that negatively affects the structure A structure is an arrangement and organization of interrelated elements in a material ...
; cataracts, leukocoria along with other developmental issues in the eye *
Occipital horn syndrome Occipital horn syndrome (OHS), formerly considered a variant of Ehlers–Danlos syndrome, is an X-linked recessive mitochondrial disease, mitochondrial and connective tissue disorder. It is caused by a deficiency in the transport of the essential m ...
; deformations in the skeleton *
Ocular albinism Ocular albinism is a form of albinism Albinism is the congenital absence of any pigmentation or colouration in a person, animal or plant, resulting in white hair, feathers, scales and skin and pink eyes in mammals, birds, reptiles, amphibian ...
; lack of pigmentation in the eye *
Ornithine transcarbamylase deficiency Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder is the final enzyme in the proximal portion of the urea cycle, re ...
; developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen * Oto-palato-digital syndrome; facial deformities, cleft palate, hearing loss * Siderius X-linked mental retardation syndrome; cleft lip and palate with mental retardation and facial dysmorphism, caused by mutations in the histone demethylase
PHF8 PHD finger protein 8 is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in ...
*
Simpson–Golabi–Behmel syndrome Simpson–Golabi–Behmel syndrome (SGBS), is a rare inherited congenital disorder A birth defect, also known as a congenital disorder, is a condition present at birth Birth is the act or process of bearing or bringing forth offspring, also ...
; coarse faces with protruding jaw and tongue, widened nasal bridge, and upturned nasal tip *
Spinal muscular atrophy Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic ...
caused by
UBE1 Ubiquitin-like modifier activating enzyme 1 (UBA1) is an enzyme which in humans is encoded by the ''UBA1'' gene. UBA1 participates in ubiquitin#ubiquitination, ubiquitination and the NEDD8 pathway for protein folding and Biodegradation, degradation ...
gene mutation; weakness due to loss of the motor neurons of the spinal cord and brainstem *
Wiskott–Aldrich syndrome Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive X-linked recessive inheritance is a mode of inheritance Inheritance is the practice of passing on private property, Title (property), titles, debts, entitlements, Privilege (law), ...
; eczema, thrombocytopenia, immune deficiency, and bloody diarrhea * X-linked severe combined immunodeficiency (SCID); infections, usually causing death in the first years of life * X-linked sideroblastic anemia; skin paleness, fatigue, dizziness and enlarged spleen and liver.


See also

*
Sex linkage Sex linked describes the sex-specific patterns of inheritance Inheritance is the practice of passing on private property Private property is a legal designation for the ownership of property by non-governmental legal entities. Private ...
*
X-linked dominant inheritance X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance Inheritance is the practice of passing on private property, titles A title is one or more words used before or after a person's n ...


References


External links


X-linked diseases
from the
Wellcome Trust The Wellcome Trust is a charitable foundation focused on health research based in London, in the United Kingdom. It was established in 1936 with legacies from the pharmaceutical magnate Henry Wellcome Sir Henry Solomon Wellcome (August 21, 185 ...
{{X-linked disorders emale X-linked disorders* https://www.nlm.nih.gov/medlineplus/ency/article/002051.htm Genetics