Autosomal dominant leukodystrophy with autonomic disease

Last updated
Autosomal dominant leukodystrophy with autonomic disease
Other namesAutosomal dominant adult-onset demyelinating leukodystrophy, ADLD, Adult-onset autosomal dominant demyelinating leukodystrophy, Adult-onset autosomal dominant leukodystrophy, Leukodystrophy, demyelinating, adult-onset, autosomal dominant, Pelizaeus-Merzbacher disease, autosomal dominant or late-onset type, Multiple sclerosis-like disorder [1]
Autosomal dominant - en.svg
Specialty Medical genetics
Symptoms Cognitive deficits, ataxia, and dysfunctions of the autonomic system
Complications Walking difficulties
Usual onsetAdulthood
DurationLifelong
Causes Genetic mutation
Diagnostic method Genetic testing
Differential diagnosis Multiple sclerosis
Preventionnone
Prognosis Bad, but quality of life can be improved with treatment
Frequencyrare, at least 70 people on Earth have been diagnosed with the condition
DeathsInevitable in patients with this condition

Autosomal dominant leukodystrophy with autonomic disease is a rare neurological condition of genetic origin which is characterized by gradual demyelination of the central nervous system which results in various impairments, including ataxia, mild cognitive disability and autonomic dysfunction. [2] [3] [4] It is part of a group of disorders called "leukodystrophies". [5] [6]

Contents

Signs and symptoms

Unlike other leukodystrophy syndromes, whose typical age of onset is during childhood, individuals with this condition typically start showing symptoms between their early 40s and late 50s, once they appear, they slowly progress in severity and new symptoms start appearing. [7]

These symptoms first start out with dysfunctions of the autonomic nervous system which result in symptoms such as abnormal functioning of both the bladder and bowel, recurrent blood pressure drops whenever patients stand up, and male erectile dysfunction. [8] [9] [10]

Rarely, anhidrosis might also occur alongside these symptoms. [9] [8] [11] [10]

After these symptoms start, movement impairments develop; they start off at the legs but then progress and move to the arms and the face, these impairments include either muscular spasticity or weakness, intention tremors, ataxia, dysmetria, and dysdiadochokinesis. [9] [8] [11] [10]

In some individuals, progressive dementia is present. [8] [9] [11]

Complications

There are various complications associated with the symptoms that ADLD causes.

Due to the ataxia and it's associated coordination impairments, people might have difficulties with movements such as walking by themselves. [12]

Treatment

Treatment is focused on the symptoms themselves

The ataxic movement impairments can be treated with walking support systems such as canes or wheelchairs, physical therapy, and speech therapy. [13]

Diagnosis

This condition is diagnosed mainly through MRIs [14] [15] and genetic testing of the LMNB gene and the areas surrounding it, [16] although symptom examination is also important for the diagnosis. [17]

Causes

This condition is caused by a duplication of the LMNB1 gene, this gene takes part in the production of the lamin B1 protein, which is essential for determining the nucleus' shape within the cells, the replication of DNA, and the way certain genes express themselves. [18] [19] [20] [21] [22] [23] [24]

When the gene is duplicated (as seen in patients with ADLD), there is an excess of lamin B1 protein, this leads to the underexpression of genes that are important for the production of myelin and an increased hardening of the nuclear envelope, which results in a progressive reduction of myelin production and maintenance as one ages. [18]

Like the name of the condition implies, this condition is inherited following an autosomal dominant pattern, which means that only one copy of a certain mutation (in this case, the duplication of the LMNB1 gene) is needed for a trait or disorder to be expressed, in familial cases, offspring have a 1 in 2, or 50% chance of inheriting a copy of said mutation from one of their affected parents. [18]

Although very rarely, this disorder can be caused by deletions near the LMNB1 gene, only one such family has been described in medical literature: they had a deletion upstream the same gene. [25]

Pathophysiology

In patients with the condition, demyelination (that is, a loss of myelin) starts occurring in both the brain and the spinal cord years before symptoms show up, this abnormality has been identified to be a contributing factor to the development of the first symptoms individuals with this condition show during the early stages of it. [8]

Phenotype-genotype

In a 2018 study done by Naomi Mezaki and 18 other colleagues, it was found that ADLD patients with a deletion near the LMNB1 gene (2 patients from a single family) started showing symptoms at an earlier age, had less autonomic dysfunctions and had more noticeable cognitive deficits than other ADLD patients with duplication of the LMNB1 gene (4 patients from 3 families). [26]

Prognosis

This condition is progressive and fatal. [27]

While the quality of life might be improved with treatment, the life expectancy can't be improved easily: individuals diagnosed with ADLD typically live for another 10 to 20 years after their diagnosis before their death. [28] [29]

Prevalence

At least 70 cases from 35 families around the world have been described in medical literature, [30] most of these were from families of Caucasian descent. [31]

History

This condition was first discovered in 1964 by E Zerbin-Rüdin et al. when they described (what they thought to be) a familial autosomal dominant variant of Pelizaeus-Merzbacher disease with onset in adulthood. [32]

In 2006, Padiath et al. found the LMNB1 duplication involved in ADLD in 4 families, of which 1 was previously described in medical literature. Haplotype studies revealed that the family mentioned beforehand and another Irish-American family shared a common ancestor. The lamin B1 protein was found to be overly expressed in brain tissues of family members affected with ADLD. [33]

See also

Related Research Articles

<span class="mw-page-title-main">Pelizaeus–Merzbacher disease</span> X-linked leukodystrophy

Pelizaeus–Merzbacher disease is an X-linked neurological disorder that damages oligodendrocytes in the central nervous system. It is caused by mutations in proteolipid protein 1 (PLP1), a major myelin protein. It is characterized by a decrease in the amount of insulating myelin surrounding the nerves (hypomyelination) and belongs to a group of genetic diseases referred to as leukodystrophies.

Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditary spastic paraparesis, familial spastic paraplegia, French settlement disease, Strumpell disease, or Strumpell-Lorrain disease. The symptoms are a result of dysfunction of long axons in the spinal cord. The affected cells are the primary motor neurons; therefore, the disease is an upper motor neuron disease. HSP is not a form of cerebral palsy even though it physically may appear and behave much the same as spastic diplegia. The origin of HSP is different from cerebral palsy. Despite this, some of the same anti-spasticity medications used in spastic cerebral palsy are sometimes used to treat HSP symptoms.

<span class="mw-page-title-main">Demyelinating disease</span> Any neurological disease in which the myelin sheath of neurons is damaged

A demyelinating disease refers to any disease affecting the nervous system where the myelin sheath surrounding neurons is damaged. This damage disrupts the transmission of signals through the affected nerves, resulting in a decrease in their conduction ability. Consequently, this reduction in conduction can lead to deficiencies in sensation, movement, cognition, or other functions depending on the nerves affected.

<span class="mw-page-title-main">Alexander disease</span> Rare genetic disorder of the white matter of the brain

Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions caused by anomalies in the myelin which protects nerve fibers in the brain. The most common type is the infantile form that usually begins during the first two years of life. Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size and seizures. The juvenile form of Alexander disease has an onset between the ages of 2 and 13 years. These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control. Adult-onset forms of Alexander disease are less common. The symptoms sometimes mimic those of Parkinson's disease or multiple sclerosis, or may present primarily as a psychiatric disorder.

<span class="mw-page-title-main">Krabbe disease</span> Medical condition

Krabbe disease (KD) is a rare and often fatal lysosomal storage disease that results in progressive damage to the nervous system. KD involves dysfunctional metabolism of sphingolipids and is inherited in an autosomal recessive pattern. The disease is named after the Danish neurologist Knud Krabbe (1885–1961).

<span class="mw-page-title-main">Leukodystrophy</span> Group of disorders characterised by degeneration of white matter in the brain

Leukodystrophies are a group of, usually, inherited disorders, characterized by degeneration of the white matter in the brain. The word leukodystrophy comes from the Greek roots leuko, "white", dys, "abnormal" and troph, "growth". The leukodystrophies are caused by imperfect growth or development of the glial cells which produce the myelin sheath, the fatty insulating covering around nerve fibers. Leukodystrophies may be classified as hypomyelinating or demyelinating diseases, respectively, depending on whether the damage is present before birth or occurs after. While all leukodystrophies are the result of genetic mutations, other demyelinating disorders have an autoimmune, infectious, or metabolic etiology.

Metachromatic leukodystrophy (MLD) is a lysosomal storage disease which is commonly listed in the family of leukodystrophies as well as among the sphingolipidoses as it affects the metabolism of sphingolipids. Leukodystrophies affect the growth and/or development of myelin, the fatty covering which acts as an insulator around nerve fibers throughout the central and peripheral nervous systems. MLD involves cerebroside sulfate accumulation. Metachromatic leukodystrophy, like most enzyme deficiencies, has an autosomal recessive inheritance pattern.

<span class="mw-page-title-main">Spinocerebellar ataxia</span> Medical condition

Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder.

<span class="mw-page-title-main">Laminopathy</span> Medical condition

Laminopathies are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. Since the first reports of laminopathies in the late 1990s, increased research efforts have started to uncover the vital role of nuclear envelope proteins in cell and tissue integrity in animals. Laminopathies are a group of degenerative diseases, other disorders associated with inner nuclear membrane proteins are known as nuclear envelopathies.

<span class="mw-page-title-main">Leukoencephalopathy with vanishing white matter</span> Neurological disease

Leukoencephalopathy with vanishing white matter is an autosomal recessive neurological disease. The cause of the disease are mutations in any of the 5 genes encoding subunits of the translation initiation factor eIF2B: EIF2B1, EIF2B2, EIF2B3, EIF2B4, or EIF2B5. The disease belongs to a family of conditions called the Leukodystrophies.

<span class="mw-page-title-main">Lamin B1</span> Protein-coding gene in the species Homo sapiens

Lamin-B1 is a protein that in humans is encoded by the LMNB1 gene.

Leukoencephalopathy with neuroaxonal spheroids (LENAS), also known as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) is an extremely rare kind of leukoencephalopathy and is classified as a neurodegenerative disease. LENAS is a cause of severe and subacute dementia that results from damage to certain areas of the brain. This damage is to a type of brain tissue called white matter and axon damage due to swellings which are termed spheroids.

Megalencephalic leukoencephalopathy with subcortical cysts is a form of hereditary CNS demyelinating disease. It belongs to a group of disorders called leukodystrophies. It is characterized by early-onset enlargement of the head (macrocephaly) as well as delayed-onset neurological deterioration to include spasticity, epilepsy, and lack of muscular coordination. MLC does not appear to be a disease that is fatal at birth or early in life despite its symptoms, although the number of patients throughout history known to have the disease is fairly limited.

<span class="mw-page-title-main">Hereditary neuropathy with liability to pressure palsy</span> Medical condition

Hereditary neuropathy with liability to pressure palsy (HNPP) is a peripheral neuropathy, a condition that affects the nerves. Pressure on the nerves can cause tingling sensations, numbness, pain, weakness, muscle atrophy and even paralysis of the affected area. In normal individuals, these symptoms disappear quickly, but in sufferers of HNPP even a short period of pressure can cause the symptoms to occur. Palsies can last from minutes or days to weeks or even months.

<span class="mw-page-title-main">Hereditary diffuse leukoencephalopathy with spheroids</span> Medical condition

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare adult onset autosomal dominant disorder characterized by cerebral white matter degeneration with demyelination and axonal spheroids leading to progressive cognitive and motor dysfunction. Spheroids are axonal swellings with discontinuous or absence of myelin sheaths. It is believed that the disease arises from primary microglial dysfunction that leads to secondary disruption of axonal integrity, neuroaxonal damage, and focal axonal spheroids leading to demyelination. Spheroids in HDLS resemble to some extent those produced by shear stress in a closed head injury with damage to axons, causing them to swell due to blockage of axoplasmic transport. In addition to trauma, axonal spheroids can be found in aged brain, stroke, and in other degenerative diseases. In HDLS, it is uncertain whether demyelination occurs prior to the axonal spheroids or what triggers neurodegeneration after apparently normal brain and white matter development, although genetic deficits suggest that demyelination and axonal pathology may be secondary to microglial dysfunction. The clinical syndrome in patients with HDLS is not specific and it can be mistaken for Alzheimer's disease, frontotemporal dementia, atypical Parkinsonism, multiple sclerosis, or corticobasal degeneration.

Roussy–Lévy syndrome, also known as Roussy–Lévy areflexic dystasia, is a rare disorder of humans that results in progressive muscle wasting. It is caused by mutation the s that code for proteins necessary for the functioning of the myelin sheath of the, affecting the conductance of nerve signals and resulting in loss of muscles' ability to move.

<span class="mw-page-title-main">Autosomal dominant cerebellar ataxia</span> Medical condition

Autosomal dominant cerebellar ataxia (ADCA) is a form of spinocerebellar ataxia inherited in an autosomal dominant manner. ADCA is a genetically inherited condition that causes deterioration of the nervous system leading to disorder and a decrease or loss of function to regions of the body.

Ying-Hui Fu is a Taiwanese-American biologist and human geneticist who has made important contributions to understanding the genetics of many neurological disorders. Her chief discoveries include describing Mendelian sleep phenotypes, identifying causative genes and mutations for circadian rhythm disorders, and characterizing genetic forms of demyelinating degenerative disorders. Fu is currently a professor of neurology at the University of California, San Francisco. She was elected to the US National Academy of Sciences in 2018.

Louis Ptáček is an American neurologist and professor who contributed greatly to the field of genetics and neuroscience. He was also an HHMI investigator from 1997 to 2018. His chief areas of research include the understanding of inherited Mendelian disorders and circadian rhythm genes. Currently, Ptáček is a neurology professor and a director of the Division of Neurogenetics in University of California, San Francisco, School of Medicine. His current investigations primarily focus on extensive clinical studies in families with hereditary disorders, which include identifying and characterizing the genes responsible for neurological variations.

Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCADN) is a rare progressive genetic disorder that primarily affects the nervous system and is characterized by sensorineural hearing loss, narcolepsy with cataplexy, and dementia later in life. People with this disorder usually start showing symptoms when they are in their early-mid adulthoods. It is a type of autosomal dominant cerebellar ataxia.

References

  1. ↑ "Autosomal dominant leukodystrophy with autonomic disease". 16 June 2022.
  2. ↑ Finnsson, J.; Melberg, A.; Raininko, R. (2013-08-01). "1H-MR spectroscopy of adult-onset autosomal dominant leukodystrophy with autonomic symptoms". Neuroradiology. 55 (8): 933–939. doi:10.1007/s00234-013-1174-5. ISSN   1432-1920. PMID   23636437. S2CID   915515.
  3. ↑ "ADLD". Global Genes. Retrieved 2022-08-16.
  4. ↑ "Pruebas genéticas - Leucodistrofia autosómica dominante con enfermedad autónoma (Autosomal dominant leukodystrophy with autonomic disease) - Gen LMNB1. - IVAMI". www.ivami.com. Retrieved 2022-08-16.
  5. ↑ "Leukodystrophy - Overview". www.brainandlife.org. Retrieved 2022-08-16.
  6. ↑ Resende, Lucas Lopes; de Paiva, Anderson Rodrigues Brandão; Kok, Fernando; da Costa Leite, Claudia; Lucato, Leandro Tavares (2019-01-01). "Adult Leukodystrophies: A Step-by-Step Diagnostic Approach". RadioGraphics. 39 (1): 153–168. doi:10.1148/rg.2019180081. ISSN   0271-5333. PMID   30620693. S2CID   58586821.
  7. ↑ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Adult onset autosomal dominant leukodystrophy". www.orpha.net. Retrieved 2022-08-16.{{cite web}}: CS1 maint: numeric names: authors list (link)
  8. 1 2 3 4 5 "Autosomal dominant leukodystrophy with autonomic disease: MedlinePlus Genetics". medlineplus.gov. Retrieved 2022-08-16.
  9. 1 2 3 4 "Autosomal dominant leukodystrophy with autonomic disease - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 2022-08-16.
  10. 1 2 3 R, M, QS, Raininko, Gosky, Padiath (2021-07-15). "LMNB1-Related Autosomal Dominant Leukodystrophy". europepmc.org. Retrieved 2022-08-16.{{cite web}}: CS1 maint: multiple names: authors list (link)
  11. 1 2 3 "Adult onset autosomal dominant leukodystrophy (ADLD)". Alex - The Leukodystrophy Charity. Retrieved 2022-08-16.
  12. ↑ "Ataxia - Symptoms and causes". Mayo Clinic. Retrieved 2022-08-16.
  13. ↑ "Ataxia - Treatment". nhs.uk. 2017-10-20. Retrieved 2022-08-16.
  14. ↑ Melberg, A.; Hallberg, L.; Kalimo, H.; Raininko, R. (2006-04-01). "MR Characteristics and Neuropathology in Adult-Onset Autosomal Dominant Leukodystrophy with Autonomic Symptoms". American Journal of Neuroradiology. 27 (4): 904–911. ISSN   0195-6108. PMC   8133955 . PMID   16611789.
  15. ↑ Finnsson, Johannes; Sundblom, Jimmy; Dahl, Niklas; Melberg, Atle; Raininko, Raili (2015-09-01). "L MNB 1-related autosomal-dominant leukodystrophy: Clinical and radiological course". Annals of Neurology. 78 (3): 412–425. doi:10.1002/ana.24452. ISSN   0364-5134. PMC   5054845 . PMID   26053668.
  16. ↑ Schuster, Jens; Sundblom, Jimmy; Thuresson, Ann-Charlotte; Hassin-Baer, Sharon; Klopstock, Thomas; Dichgans, Martin; Cohen, Oren S.; Raininko, Raili; Melberg, Atle; Dahl, Niklas (2011-02-01). "Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms". Neurogenetics. 12 (1): 65–72. doi:10.1007/s10048-010-0269-y. ISSN   1364-6753. PMID   21225301. S2CID   31170330.
  17. ↑ Terlizzi, Rossana; Calandra-Buonaura, Giovanna; Zanigni, Stefano; Barletta, Giorgio; Capellari, Sabina; Guaraldi, Pietro; Donadio, Vincenzo; Cason, Ernesto; Contin, Manuela; Poda, Roberto; Tonon, Caterina; Sambati, Luisa; Gallassi, Roberto; Liguori, Rocco; Lodi, Raffaele (2016-02-01). "A longitudinal study of a family with adult-onset autosomal dominant leukodystrophy: Clinical, autonomic and neuropsychological findings". Autonomic Neuroscience. 195: 20–26. doi:10.1016/j.autneu.2016.02.005. ISSN   1566-0702. PMID   26896090. S2CID   5864535.
  18. 1 2 3 "LMNB1 gene: MedlinePlus Genetics". medlineplus.gov. Retrieved 2022-08-16.
  19. ↑ "Adult Onset Autosomal Dominant (ADLD) - Causes, Treatment & Symptoms". Hunter's Hope. Retrieved 2022-08-16.
  20. ↑ Lynch, David S.; Wade, Charles; Paiva, Anderson Rodrigues Brandão de; John, Nevin; Kinsella, Justin A.; Merwick, Áine; Ahmed, Rebekah M.; Warren, Jason D.; Mummery, Catherine J.; Schott, Jonathan M.; Fox, Nick C.; Houlden, Henry; Adams, Matthew E.; Davagnanam, Indran; Murphy, Elaine (2019-05-01). "Practical approach to the diagnosis of adult-onset leukodystrophies: an updated guide in the genomic era". Journal of Neurology, Neurosurgery & Psychiatry. 90 (5): 543–554. doi:10.1136/jnnp-2018-319481. ISSN   0022-3050. PMC   6581077 . PMID   30467211.
  21. ↑ Sabetrasekh, Vanderver, Parisa, Adeline (2018-06-01). "Autosomal Dominant Leukodystrophy with Autonomic Disease Synonyms: ADLD, Adult-Onset Autosomal Dominant Leukodystrophy with Autonomic Symptoms, Autosomal Dominant Adult-Onset Demyelinating Leukodystrophy, LMNB1-Related Adult-Onset Autosomal Dominant Leukodystrophy. Bookshelf ID: NBK338165, PMID 26749591". ResearchGate.{{cite web}}: CS1 maint: multiple names: authors list (link)
  22. ↑ "ADLD". encyclopedia.pub. Retrieved 2022-08-16.
  23. ↑ "leukodystrophy, demyelinating, adult-onset, autosomal dominant".
  24. ↑ "Autosomal Dominant Leukodystrophy, Adult Onset". www.nemours.org. Retrieved 2022-08-16.
  25. ↑ Giorgio, Elisa; Robyr, Daniel; Spielmann, Malte; Ferrero, Enza; Di Gregorio, Eleonora; Imperiale, Daniele; Vaula, Giovanna; Stamoulis, Georgios; Santoni, Federico; Atzori, Cristiana; Gasparini, Laura; Ferrera, Denise; Canale, Claudio; Guipponi, Michel; Pennacchio, Len A. (2015-06-01). "A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)". Human Molecular Genetics. 24 (11): 3143–3154. doi:10.1093/hmg/ddv065. ISSN   1460-2083. PMC   4424952 . PMID   25701871.
  26. ↑ Mezaki, Naomi; Miura, Takeshi; Ogaki, Kotaro; Eriguchi, Makoto; Mizuno, Yuri; Komatsu, Kenichi; Yamazaki, Hiroki; Suetsugi, Natsuki; Kawajiri, Sumihiro; Yamasaki, Ryo; Ishiguro, Takanobu; Konno, Takuya; Nozaki, Hiroaki; Kasuga, Kensaku; Okuma, Yasuyuki (2018-12-01). "Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy". Neurology: Genetics. 4 (6): e292. doi:10.1212/NXG.0000000000000292. ISSN   2376-7839. PMC   6340331 . PMID   30697589.
  27. ↑ Padiath, Quasar S. (2019). "Autosomal Dominant Leukodystrophy: A Disease of the Nuclear Lamina". Frontiers in Cell and Developmental Biology. 7: 41. doi: 10.3389/fcell.2019.00041 . ISSN   2296-634X. PMC   6435485 . PMID   30949481.
  28. ↑ Association, United Brain. "Autosomal Dominant Leukodystrophy (ADLD)". United Brain Association. Retrieved 2022-08-16.
  29. ↑ Zhang, Yanyan; Li, Jie; Bai, Rong; Wang, Jianping; Peng, Tao; Chen, Lijie; Wang, Jingtao; Liu, Yanru; Tian, Tian; Lu, Hong (2019). "LMNB1-Related Adult-Onset Autosomal Dominant Leukodystrophy Presenting as Movement Disorder: A Case Report and Review of the Literature". Frontiers in Neuroscience. 13: 1030. doi: 10.3389/fnins.2019.01030 . ISSN   1662-453X. PMC   6816284 . PMID   31695592.
  30. ↑ "Entry - #169500 - LEUKODYSTROPHY, DEMYELINATING, ADULT-ONSET, AUTOSOMAL DOMINANT; ADLD - OMIM". www.omim.org. Retrieved 2022-08-16.
  31. ↑ Lin, Shu-Ting; Ptáček, Louis J.; Fu, Ying-Hui (2011-01-26). "Adult-Onset Autosomal Dominant Leukodystrophy: Linking Nuclear Envelope to Myelin". Journal of Neuroscience. 31 (4): 1163–1166. doi:10.1523/JNEUROSCI.5994-10.2011. ISSN   0270-6474. PMC   3078713 . PMID   21273400.
  32. ↑ Zerbin-Rüdin, E.; Peiffer, J. (1964). "[Genetic contribution to the problem of the late form of Pelizaeus-Merzbacher disease]". Humangenetik. 1 (2): 107–122. doi:10.1007/BF00389627. ISSN   0018-7348. PMID   5869474. S2CID   34057578.
  33. ↑ Padiath, Quasar S.; Saigoh, Kazumasa; Schiffmann, Raphael; Asahara, Hideaki; Yamada, Takeshi; Koeppen, Anulf; Hogan, Kirk; Ptácek, Louis J.; Fu, Ying-Hui (2006-10-01). "Lamin B1 duplications cause autosomal dominant leukodystrophy". Nature Genetics. 38 (10): 1114–1123. doi:10.1038/ng1872. ISSN   1061-4036. PMID   16951681. S2CID   25336497.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.