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Mucolipidosis IV

, MD, MHSc, , PhD, , MD, and , PhD.

Author Information
, MD, MHSc
Director, Institute of Metabolic Disease
Baylor Research Institute
Dallas, Texas
, PhD
MGH Center for Human Genetic Research / Harvard Medical School
Boston, Massachusetts
, MD
National Eye Institute
National Institutes of Health
Bethesda, Maryland
, PhD
Section on Molecular Neurogenetics
Medical Genetics Branch
National Human Genome Research Institute
National Institutes of Health
Bethesda, Maryland

Initial Posting: ; Last Update: July 20, 2010.

Summary

Disease characteristics. Mucolipidosis IV is characterized by severe psychomotor delay evident by the end of the first year of life and slowly progressive visual impairment during the first decade as a result of a combination of corneal clouding and retinal degeneration. By the end of the first decade of life and certainly by their early teens, all individuals with typical mucolipidosis IV have severe visual impairment as a result of retinal degeneration. Neurodegeneration is thought to occur in no more than 15% of individuals. About 5% of individuals have atypical mucolipidosis IV, often manifest as less severe psychomotor retardation and/or eye findings. About 70% of individuals with mucolipidosis IV are of Ashkenazi Jewish heritage.

Diagnosis/testing. Mucolipidosis IV is suspected in individuals with typical clinical findings and elevated plasma gastrin concentration or polymorphic lysosomal inclusions in skin or conjunctival biopsy. Molecular genetic testing of MCOLN1, the only gene known to be associated with mucolipidosis IV, confirms the diagnosis in most individuals. Two mutations, c.406-2A>G and g.511_6943del, account for 95% of mutations in individuals of Ashkenazi Jewish heritage.

Management. Treatment of manifestations: Speech therapy; physical therapy for spasticity and ataxia; ankle-foot orthotics (AFOs) as needed; antiepileptic drugs (AED) as needed; topical lubricating eye drops, artificial tears, gels, or ointments for ocular irritation; surgical correction of strabismus; high-contrast black and white materials for those with visual impairment.

Prevention of secondary complications: Physical therapy to prevent permanent joint contractures; oral iron to prevent iron deficiency anemia from poor absorption of dietary iron.

Genetic counseling. Mucolipidosis IV is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible for families in which both disease-causing mutations have been identified.

Diagnosis

Clinical Diagnosis

Mucolipidosis IV should be suspected in any individual with the following:

  • Early onset of developmental delay whether static, as in cerebral palsy, or progressively declining with loss of previously acquired cognitive and motor abilities [Altarescu et al 2002]
  • Dystrophic retinopathy with or without corneal clouding [Smith et al 2002]

Testing

Plasma gastrin concentration is elevated in virtually all individuals with mucolipidosis IV (mean 1507 pg/mL; range 400-4100 pg/mL) (normal 0-200 pg/mL) [Schiffmann et al 1998, Altarescu et al 2002].

Biopsy of skin or conjunctiva shows accumulation of abnormal lamellar membrane structures and amorphous cytoplasmic inclusions in diverse cell types. Note: In the past, these findings were used to confirm the diagnosis of mucolipidosis IV [Bargal et al 2002]; more recently, however, demonstration of typical vacuolation by PAS staining of conjunctival cells obtained with a swab has been used for diagnosis [Smith et al 2002].

Molecular Genetic Testing

Gene. MCOLN1 is the only gene known to be associated with mucolipidosis IV.

Clinical testing

Table 1. Summary of Molecular Genetic Testing Used in Mucolipidosis IV

Gene 1Test MethodMutations Detected 2Mutation Detection Frequency by Test Method 3
Ashkenazi JewishNon-Ashkenazi Jewish
MCOLN1Targeted mutation analysisc.406-2A>G, g.511_6943del 495%6%-10%
Sequence analysisSequence variants 5, 699% 599%
Deletion / duplication analysis 7Exonic or whole-gene deletionsUnknown Unknown

1. See Table A. Genes and Databases for chromosome locus and protein name.

2. See Molecular Genetics for information on allelic variants.

3. The ability of the test method used to detect a mutation that is present in the indicated gene

4. The breakpoints for this deletion can vary slightly; see HGMD.

5. Includes the two mutations identified by targeted mutation analysis

6. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations; typically, exonic or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

7. Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

Testing Strategy

To establish/confirm the diagnosis in a proband

Carrier testing for at-risk relatives requires prior identification of the disease-causing mutations in an affected family member.

Note: Carriers are heterozygous for an autosomal recessive disorder and are not at risk of developing the disorder.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutations in the family.

Clinical Description

Natural History

Mucolipidosis IV is a neurodevelopmental disorder that is also neurodegenerative in about 15% of individuals. The phenotype in affected individuals can be considered either typical (~95% of individuals) or atypical (~5% of individuals) [Altarescu et al 2002]. Although individuals with mucolipidosis IV typically survive to adulthood, it is believed that the life expectancy is reduced compared to healthy individuals.

Typical mucolipidosis IV. The most common presentation is severe psychomotor delay by the end of the first year of life in a child who is subsequently noted to have visual impairment caused by a combination of corneal clouding and retinal degeneration.

Psychomotor development is usually limited to few or no words and poor hand use [Altarescu et al 2002]; some may develop the ability to sit independently or crawl. Most individuals do not achieve independent walking [Altarescu et al 2002]; a few have learned to walk with the aid of a walker [Altarescu et al 2002].

Receptive language is better than expressive language; some individuals have used up to 50 signs to communicate.

Neurologic examination typically reveals severe dysarthria or anarthria, slow chewing, slow eating and swallowing, and spastic diplegia or quadriplegia [Altarescu et al 2002]. Individuals may be hypotonic, but tendon reflexes are usually hyperactive.

Neurologic deficits generally remain static during the first three decades of life [Altarescu et al 2002], although some individuals have neurologic deterioration.

MRI typically shows hypoplasia of the corpus callosum with absent rostrum and a dysplastic or absent splenium, signal abnormalities in the white matter on T1-weighted images, and increased ferritin deposition in the thalamus and basal ganglia. Atrophy of the cerebellum is observed in older individuals [Frei et al 1998].

Epileptiform discharges are common but are infrequently associated with clinical seizures [Siegel et al 1998].

Individuals with typical mucolipidosis IV have superficial corneal clouding that is bilateral, symmetric, and most visible in the central cornea [Smith et al 2002]. The corneal opacification is limited to the epithelium without stromal involvement or edema [Authors, personal observation], early reports of stromal abnormalities notwithstanding. On occasion, corneal clouding is the feature that prompts medical evaluation.

Painful episodes consistent with corneal erosions are common, but appear to decrease in frequency and severity with age.

Vision may be close to normal at a young age; over the first decade of life, progressive retinal degeneration with varying degrees of vascular attenuation, retinal pigment epithelial changes, and optic nerve pallor result in further decrease in vision [Siegel et al 1998, Altarescu et al 2002, Pradhan et al 2002, Smith et al 2002]. Bilateral bull's eye maculopathy was observed in one individual [Smith et al 2002]. Visual acuity is difficult to test in most individuals with mucolipidosis IV, but is decreased in almost all persons over age five years. Virtually all individuals with mucolipidosis IV develop severe visual impairment by their early teens as a result of the retinal degeneration.

Other ocular findings are strabismus (>50% of individuals), nystagmus, ptosis, and cataract [Bach 2001, Smith et al 2002]. The pupillary response to light is usually sluggish without evidence of relative afferent pupillary defect [Smith et al 2002].

Iron deficiency occurs in about 50% and iron deficiency anemia, which is usually well tolerated, occurs in about 10% of individuals [Altarescu et al 2002].

The achlorhydria is asymptomatic.

The face is not typically coarse.

Affected individuals do not have hepatosplenomegaly or specific skeletal abnormalities.

Atypical and mild mucolipidosis IV. Individuals with atypical mucolipidosis IV are less severely affected than individuals with typical mucolipidosis IV or have one organ system disproportionately affected [Altarescu et al 2002].

Some individuals attain the ability to walk independently. They develop slowly progressive ataxia, have mild eye abnormalities, and are usually of non-Ashkenazi Jewish descent [Altarescu et al 2002].

Some present with a congenital myopathy with significant generalized hypotonia and elevated serum muscle creatine kinase concentration.

Some present with static (non-progressive) motor and cognitive delay and minimal ocular abnormalities.

  • One female who presented with progressive visual impairment with corneal clouding with the appearance of cornea verticillata, retinopathy, normal psychomotor development, and behavioral abnormalities developed unstable gait in her twenties [Altarescu et al 2002].
  • Two other individuals with no neurologic deficit were diagnosed based on ocular findings [Dobrovolny et al 2007, Goldin et al 2008]. The patients had all the other typical features of mucolipidosis IV including achlorhydria and autofluorescent inclusions in cultured skin fibroblasts [Dobrovolny et al 2007, Goldin et al 2008].

Genotype-Phenotype Correlations

Ashkenazi Jewish individuals usually have the most severe form of the disease.

A missense mutation that creates a new preferred splice site of MCOLN1 (c.1406A>G) discovered in a Canadian family from Newfoundland causes an atypical form of mucolipidosis IV, in which affected individuals walk independently and have better communicative skills [Altarescu et al 2002]. Missense mutations were found in the loop between the first and second transmembrane domain, one in the lipase domain, and one eliminating one of the four cysteines in the loop, possibly reducing the stability of mucolipin-1. Individuals with these mutations had a mild phenotype, an independent ataxic gait, and the ability to use their hands to feed themselves.

The typical, rather severe presentation associated with the c.694A>C mutation (p.Thr232Pro) in the same region may be explained by the fact that the mutated protein does not reach the endocytic compartment and accumulates in the endoplasmic reticulum [Manzoni et al 2004].

In several individuals from the southeast United States, a p.Asp362Tyr amino acid change was identified in the third transmembrane domain. This mutation was associated with a slower progression of the retinal disease and a relatively mild neurologic phenotype, although membrane preparations containing mucolipin-1 with this mutation had no channel activity [Raychowdhury et al 2004].

Several mutations were discovered in the fourth transmembrane domain, including p.Phe408del, which causes the mildest mucolipidosis IV phenotype known [Altarescu et al 2002]. The protein construct containing this mutation still functions as a channel in liposome preparations and only displays a deficiency in regulation [Raychowdhury et al 2004].

Several other mutations were discovered in the area of the presumed channel pore between the fifth and sixth transmembrane domain. Most of those were associated with a severe mucolipidosis IV phenotype (Table 3) [Altarescu et al 2002].

Nomenclature

Mucolipidosis IV was classified as a mucolipidosis because of the initial impression of simultaneous storage of lipids and water-soluble substances.

Prevalence

The combined carrier frequency of the two Ashkenazi Jewish mutations ranges from 1:100 to 1:127 in individuals of Ashkenazi Jewish descent [Bargal et al 2001, Edelmann et al 2002], although in a small group of 123 individuals, other investigators found a higher frequency [Wang et al 2001].

Prior to the availability of molecular diagnosis of mucolipidosis IV, individuals with atypical mucolipidosis IV were thought to have cerebral palsy, suggesting that mucolipidosis IV is underdiagnosed.

Differential Diagnosis

Because of the relatively static nature of the neurologic abnormality in mucolipidosis IV, individuals considered to have "cerebral palsy" should be evaluated for mucolipidosis IV.

The neurologic abnormalities and the finding of widespread storage material in tissue biopsy could suggest other lysosomal storage disorders including mucolipidosis type I, mucolipidosis type II, and the mucopolysaccharidoses.

The finding of white matter abnormalities and a thin dysplastic corpus callosum could suggest other inherited hypomyelinating leukodystrophies such as sialic acid storage disease (Salla disease). (See Free Sialic Acid Storage Disorders.)

Corneal clouding also occurs in the mucopolysaccharidoses (MPSI, MPSIII, MPSIVA, MPSIVB, MPSVI), in mucolipidosis II and mucolipidosis III (see Mucolipidosis III Alpha/Beta, Mucolipidosis III Gamma), and in GM1 gangliosidosis. Cornea verticillata (without retinal dystrophy) occurs in Fabry disease.

The retinal dystrophy of mucolipidosis IV is similar to that observed in the neuronal ceroid-lipofuscinoses and other genetic disorders with retinal degeneration such as Bardet-Biedl syndrome and Alström syndrome.

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with mucolipidosis IV, the following evaluations are recommended:

  • Ophthalmic examination
  • Brain MRI
  • Iron studies
  • Neurologic evaluation, including EEG

Treatment of Manifestations

The following treatment is appropriate:

  • Speech therapy
  • Physical therapy and rehabilitation for motor dysfunction (mainly spasticity and ataxia)
  • Ankle-foot orthotics in individuals with hypotonia and weakness of ankle dorsiflexion
  • Antiepileptic drugs (AEDs)
  • Topical lubricating eye drops, artificial tears, gels, or ointments for management of the intermittent ocular irritation seen frequently in younger children
  • Surgical correction of strabismus
  • High-contrast black and white materials for those with visual impairment

Prevention of Secondary Complications

Physical therapy and rehabilitation can help prevent permanent joint contractures.

An oral iron preparation such as a ferrous sulfate is indicated for treatment of iron deficiency anemia resulting from poor absorption of dietary iron.

Surveillance

Annual follow up with a generalist is appropriate.

Agents/Circumstances to Avoid

Chloroquine may be contraindicated, based on published research in patient cultured skin fibroblasts [Goldin et al 1999].

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Other

Corneal transplantation has not been successful because the donor corneal epithelium is eventually replaced by the abnormal host epithelium.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Mucolipidosis IV is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected child are obligate heterozygotes and therefore carry one mutant allele.
  • Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.
  • Heterozygotes (carriers) are asymptomatic.

Offspring of a proband. Individuals with mucolipidosis IV do not reproduce. No information is available regarding the ability of individuals with mild disease to reproduce.

Other family members of a proband. Each sib of the proband's parents is at a 50% risk of being a carrier.

Carrier Detection

Carrier testing for at-risk family members is possible if both disease-causing mutations have been identified in an affected family member.

Population Screening

Because of the high carrier rate in individuals of Ashkenazi Jewish descent and the availability of premarital, preconception, and prenatal genetic counseling as well as prenatal diagnosis, mutation analysis of MCOLN1 is often included in the panel of "Ashkenazi Jewish mutations" offered to individuals interested in preconception or prenatal risk assessment modification. Through this type of screening, couples in which both partners are carriers can be made aware of their status and risks before having affected children. Through genetic counseling and the option of prenatal testing, such families can, if they choose, bring to term only those pregnancies in which the fetus is unaffected.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

If the disease-causing mutations have been identified in the family or carrier status has been confirmed in both parents, prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis (usually performed at ~15-18 weeks’ gestation) or chorionic villus sampling (usually performed at ~10-12 weeks’ gestation).

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the disease-causing mutations have been identified.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Mucolipidosis IV Foundation
    719 East 17th Street
    Brooklyn NY 11230
    Phone: 718-434-5067
    Email: www@ml4.org
  • National MPS Society
    PO Box 14686
    Durham NC 27709-4686
    Phone: 877-677-1001 (toll-free); 919-806-0101
    Fax: 919-806-2055
    Email: info@mpssociety.org
  • Society for Mucopolysaccharide Diseases (MPS)
    MPS House Repton Place
    White Lion Road
    Amersham Buckinghamshire HP7 9LP
    United Kingdom
    Phone: +44 0845 389 9901
    Email: mps@mpssociety.co.uk
  • Chicago Center for Jewish Genetic Disorders
    Ben Gurion Way
    30 South Wells Street
    Chicago IL 60606
    Phone: 312-357-4718
    Email: jewishgeneticsctr@juf.org

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A. Mucolipidosis IV: Genes and Databases

Gene SymbolChromosomal LocusProtein NameLocus SpecificHGMD
MCOLN119p13​.2Mucolipin-1MCOLN1 homepage - Mendelian genesMCOLN1

Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B. OMIM Entries for Mucolipidosis IV (View All in OMIM)

252650MUCOLIPIDOSIS IV
605248MUCOLIPIN 1; MCOLN1

Molecular Genetic Pathogenesis

The lysosomal storage of lipids and water-soluble substances in mucolipidosis IV is attributed to a transport defect in the late steps of endocytosis resulting from abnormal membrane components of endosomes. Endosomes shuttle lipids and proteins between the plasma membrane and the various cellular organelles. Nutrients bound to lysosomes for processing would be retained in these transition vesicles. Alternatively it could indicate an increased rate of membrane recycling resulting from rapid degradation of malfunctioning protein complexes at the plasma membrane. Inability of cells to compensate for the missing cation channel function causes the defect in organization of white matter in the brain and reduces maintenance of cells in the retina and optic nerve. Inability to secrete gastric acid may be directly related to a defect in the operation of the acid-secreting H+K+ ATPase in stomach parietal cells.

In C. elegans a mutation in an ABC transporter gene compensates for mucolipin deficiency and leads to viable worms, indicating that loss of a regulatory effect of mucolipin on the activity of the transporter is probably the cause of death in mucolipin-deficient worms [Schaheen et al 2006].

Normal allelic variants. MCOLN1 spans 12,300 base pairs and contains 14 exons. In humans, no expressed splice variants are known. A single-nucleotide polymorphism, c.984C>T (p.Asn328Asn), results in no amino acid change (reference sequence NM_020533.1).

Pathologic allelic variants. A variety of mutations cause mucolipidosis IV, including splice mutations, small and large deletions and insertions, and point mutations that either cause stop codons or amino-acid changes in MCOLN1 (Table 3). The two most prevalent mutations cause the majority of mucolipidosis IV in the Ashkenazi Jewish population. One is the splice mutation c.406-2A>G, which prevents splicing of mucolipin-1 mRNA at exon 4, resulting in a mix of unstable aberrant mRNA species. The second, g.511_6943del, is a deletion mutation that eliminates 6434 bp of DNA, including the first five exons and part of exon 6 of MCOLN1. A Polish individual with a non-Jewish haplotype was found to be heterozygous for this mutation [Sun et al 2000].

Missense mutations were found in the loop between the first and second transmembrane domain, one in the lipase domain and one eliminating the four cysteines in the loop, possibly reducing the stability of mucolipin. See Table 2 (pdf) for a summary of additional mutations not discussed in this review. For more information, see Table A.

Table 3. Selected MCOLN1 Pathologic Allelic Variants

Protein ChangeDNA ChangeReference Sequence Alias 1
c.406-2A>GNM_020533​.2
AF287270
IVS3-2A>G
g.511_6943del AF287270 6.4-kb deletion
p.Thr232Pro c.694A>CNM_020533​.2
p.Asp362Tyr c.1084G>T
p.Phe408del c.1221_1223delCTT
p.Phe454_Asn569del c.1406A>G 2g.9107A>G
See footnote 3c.1704A>T 3
p.Ala539Profs*41 4c.1615delG 4

Note on variant classification: Variants listed in the table have been provided by the author(s). GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (www​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1. Variant designation that does not conform to current naming conventions

2. Base pair transition creates a new preferred splice acceptor site that results in a frameshift.

3. Near the donor site of intron 13; creates an alternative donor splice site that results in a frameshift [Dobrovolny et al 2007]

4. Goldin et al [2008]

Normal gene product. Mucolipin-1 is a 580-amino acid protein that is a member of the transient receptor potential (TRP) family. Proteins of this family are generally considered Ca2+ channels. Mucolipin-1 has a high homology to mucolipin-2 and mucolipin-3. It also shows homologies to polycystin-2, the product of PKD2, one of two genes associated with autosomal dominant polycystic kidney disease. Mucolipin-1 and polycystin-2 function as nonselective cation channels in heterologous expression systems [Fares & Greenwald 2001, LaPlante et al 2002, Slaugenhaupt 2002, Raychowdhury et al 2004, Treusch et al 2004].

Abnormal gene product. Most mutations are null alleles resulting in no gene product. When an abnormal gene product exists, it is a nonfunctional protein.

References

Literature Cited

  1. Altarescu G, Sun M, Moore DF, Smith JA, Wiggs EA, Solomon BI, Patronas NJ, Frei KP, Gupta S, Kaneski CR, Quarrell OW, Slaugenhaupt SA, Goldin E, Schiffmann R. The neurogenetics of mucolipidosis type IV. Neurology. 2002;59:306–13. [PubMed: 12182165]
  2. Bach G. Mucolipidosis type IV. Mol Genet Metab. 2001;73:197–203. [PubMed: 11461186]
  3. Bargal R, Avidan N, Ben-Asher E, Olender Z, Zeigler M, Frumkin A, Raas-Rothschild A, Glusman G, Lancet D, Bach G. Identification of the gene causing mucolipidosis type IV. Nat Genet. 2000;26:118–23. [PubMed: 10973263]
  4. Bargal R, Avidan N, Olender T, Ben Asher E, Zeigler M, Raas-Rothschild A, Frumkin A, Ben-Yoseph O, Friedlender Y, Lancet D, Bach G. Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population. Hum Mutat. 2001;17:397–402. [PubMed: 11317355]
  5. Bargal R, Goebel HH, Latta E, Bach G. Mucolipidosis IV: novel mutation and diverse ultrastructural spectrum in the skin. Neuropediatrics. 2002;33:199–202. [PubMed: 12368990]
  6. Bassi MT, Manzoni M, Monti E, Pizzo MT, Ballabio A, Borsani G. Cloning of the gene encoding a novel integral membrane protein, mucolipidin-and identification of the two major founder mutations causing mucolipidosis type IV. Am J Hum Genet. 2000;67:1110–20. [PMC free article: PMC1288553] [PubMed: 11013137]
  7. Edelmann L, Dong J, Desnick RJ, Kornreich R. Carrier screening for mucolipidosis type IV in the American Ashkenazi Jewish population. Am J Hum Genet. 2002;70:1023–7. [PMC free article: PMC379096] [PubMed: 11845410]
  8. Fares H, Greenwald I. Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog. Nat Genet. 2001;28:64–8. [PubMed: 11326278]
  9. Dobrovolny R, Liskova P, Ledvinova J, Poupetova H, Asfaw B, Filipec M, Jirsova K, Kraus J, Elleder M. Mucolipidosis IV: report of a case with ocular restricted phenotype caused by leaky splice mutation. Am J Ophthalmol. 2007;143:663–71. [PubMed: 17239335]
  10. Frei KP, Patronas NJ, Crutchfield KE, Altarescu G, Schiffmann R. Mucolipidosis type IV: characteristic MRI findings. Neurology. 1998;51:565–9. [PubMed: 9710036]
  11. Goldin E, Caruso RC, Benko W, Kaneski CR, Stahl S, Schiffmann R. Isolated ocular disease is associated with decreased mucolipin-1 channel conductance. Invest Ophthalmol Vis Sci. 2008;49:3134–42. [PubMed: 18326692]
  12. Goldin E, Cooney A, Kaneski CR, Brady RO, Schiffmann R. Mucolipidosis IV consists of one complementation group. Proc Natl Acad Sci U S A. 1999;96:8562–6. [PMC free article: PMC17556] [PubMed: 10411915]
  13. Goldin E, Stahl S, Cooney AM, Kaneski CR, Gupta S, Brady RO, Ellis JR, Schiffmann R. Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV. Hum Mutat. 2004;24:460–5. [PubMed: 15523648]
  14. LaPlante JM, Falardeau J, Sun M, Kanazirska M, Brown EM, Slaugenhaupt SA, Vassilev PM. Identification and characterization of the single channel function of human mucolipin-1 implicated in mucolipidosis type IV, a disorder affecting the lysosomal pathway. FEBS Lett. 2002;532:183–7. [PubMed: 12459486]
  15. Manzoni M, Monti E, Bresciani R, Bozzato A, Barlati S, Bassi MT, Borsani G. Overexpression of wild-type and mutant mucolipin proteins in mammalian cells: effects on the late endocytic compartment organization. FEBS Lett. 2004;567:219–24. [PubMed: 15178326]
  16. Pradhan SM, Atchaneeyasakul LO, Appukuttan B, Mixon RN, McFarland TJ, Billingslea AM, Wilson DJ, Stout JT, Weleber RG. Electronegative electroretinogram in mucolipidosis IV. Arch Ophthalmol. 2002;120:45–50. [PubMed: 11786056]
  17. Raychowdhury MK, Gonzalez-Perrett S, Montalbetti N, Timpanaro GA, Chasan B, Goldmann WH, Stahl S, Cooney A, Goldin E, Cantiello HF. Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel. Hum Mol Genet. 2004;13:617–27. [PubMed: 14749347]
  18. Schaheen L, Dang H, Fares H. Basis of lethality in C. elegans lacking CUP-5, the Mucolipidosis Type IV orthologue. Dev Biol. 2006;293:382–91. [PubMed: 16530747]
  19. Schiffmann R, Dwyer NK, Lubensky IA, Tsokos M, Sutliff VE, Latimer JS, Frei KP, Brady RO, Barton NW, Blanchette-Mackie EJ, Goldin E. Constitutive achlorhydria in mucolipidosis type IV. Proc Natl Acad Sci U S A. 1998;95:1207–12. [PMC free article: PMC18720] [PubMed: 9448310]
  20. Siegel H, Frei K, Greenfield J, Schiffmann R, Sato S. Electroencephalographic findings in patients with mucolipidosis type IV. Electroencephalogr Clin Neurophysiol. 1998;106:400–3. [PubMed: 9680151]
  21. Slaugenhaupt SA. The molecular basis of mucolipidosis type IV. Curr Mol Med. 2002;2:445–50. [PubMed: 12125810]
  22. Smith JA, Chan CC, Goldin E, Schiffmann R. Noninvasive diagnosis and ophthalmic features of mucolipidosis type IV. Ophthalmology. 2002;109:588–94. [PubMed: 11874766]
  23. Sun M, Goldin E, Stahl S, Falardeau JL, Kennedy JC, Acierno JS, Bove C, Kaneski CR, Nagle J, Bromley MC, Colman M, Schiffmann R, Slaugenhaupt SA. Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel. Hum Mol Genet. 2000;9:2471–8. [PubMed: 11030752]
  24. Treusch S, Knuth S, Slaugenhaupt SA, Goldin E, Grant BD, Fares H. Caenorhabditis elegans functional orthologue of human protein h-mucolipin-1 is required for lysosome biogenesis. Proc Natl Acad Sci U S A. 2004;101:4483–8. [PMC free article: PMC384773] [PubMed: 15070744]
  25. Wang ZH, Zeng B, Pastores GM, Raksadawan N, Ong E, Kolodny EH. Rapid detection of the two common mutations in Ashkenazi Jewish patients with mucolipidosis type IV. Genet Test. 2001;5:87–92. [PubMed: 11551108]

Chapter Notes

Revision History

  • 20 July 2010 (me) Comprehensive update posted live
  • 6 June 2007 (me) Comprehensive update posted to live Web site
  • 1 December 2005 (rs) Revision: sequence analysis no longer clinically available
  • 28 January 2005 (me) Review posted to live Web site
  • 16 August 2004 (rs) Original submission
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