1.

Sebuah lisosom yang baru terbentuk belum akan terlibat dalam beberapa aktifitas seluler
dinamakan lisosom primer; yang lainnya digolongkan sebagai lisosom sekunder
( vakuola pencernaan, vakuola residu, vakuola autophagic, dll).
2. Satu biomembran mengelilingi matrik enzim yang kaya.
3. Kepadatan matriks bervariasi: relative homogeny pada lisosom primer; pada lisosom
sekunder matriks menganduk banyak masukkan ( bagian dari organel pencernaan atau
bakteri, dll).
4. Matriks terdiri dari banyak enzim hidrolitik yang berbeda.
5. Enzim bias mencerna setiap komponen sel .
6. Asam Phosphat = klasik, penanda enzim; digunakan untuk menunjukkan kehadiran dari
lisosom di jaringan hewan.
Enzim lisosom disintesis oleh Rtikulum Endoplasma Kasar dan dibungkus ke vesikula
prelisosom oleh aparatus golgi.

Gabungan Autophagosome-lisosom di neuron memerlukan INPP5E, sebuah protein yang

terkait dengan syndrome Joubert

Autophagy adalah tahapan lalu lintas membran. Sebaliknya pembentukan autophagosome,

mendasari mekanisme gabungan tetap autophagosome-lysosome yang sebagian besar tidak
diketahui. Disini, kami akan menggambarkan cerita regulasi autophagy, inositol polyphosphate5-phosphatase E (INPP5E), melibatkan proses penggabungan autophagosome-lysosome. Di sel
neuron. INPP5E merobohkan dengan kuat autophagy penghambat dengan merusak tahap
penggabungan. Pecahan dari INPP5E ditempatkan di lisosom, dan membrane jangkar dan
aktifitas enzymatic diperlukan untuk autophagy. INPP5E menurunkan lisosom
phosphatidylinositol 3,5-bifosfat (PI (3,5) P2), salah satu substrat fosfatase, yaitu melawan
cortactinmediated stabilisasi filamen aktin pada lisosom. Lisosom membutuhkan filamen aktin
pada permukaannya untuk bergabung dengan autophagosomes. INPP5E adalah salah satu gen
yang bertanggung jawab untuk Joubert sindrom, kelainan otak langka, dan mutasi yang
ditemukan di
pasien dengan penyakit ini disebabkan cacat pada autophagy. Diambil bersama-sama, data kami
menunjukkan peran novel phosphoinositide pada lisosom dan hubungan antara autophagy dan
saraf penyakit.

Result
INPP5E, sebuah komponen baru dari autofagi tahap selanjutnya

Joubert Syndrome
NORD gratefully acknowledges Joseph G. Gleeson, MD, Professor, Neurogenetics Laboratory,
Department of Neurosciences and Pediatrics; Investigator, Howard Hughes Medical Institute,
University of California, San Diego, for assistance in the preparation of this report.
Synonyms of Joubert Syndrome

cerebellooculorenal syndrome 1; CORS1

cerebelloparenchchymal disorder IV familial

Joubert-Bolthauser syndrome

General Discussion
Joubert syndrome is an autosomal recessive genetic disorder that affects the area of the brain that
controls balance and coordination. This condition is characterized by a specific finding on an
MRI called a "molar tooth sign" in which the cerebellar vermis of the brain is absent or
underdeveloped and the brain stem is abnormal. The most common features of Joubert syndrome
are lack of muscle control (ataxia), abnormal breathing patterns (hyperpnea), sleep apnea,
abnormal eye and tongue movements and low muscle tone.
Signs & Symptoms
Many of the clinical symptoms of Joubert syndrome are apparent in infancy and most affected
children have delays in gross motor milestones. The most common features are lack of muscle
control (ataxia), abnormal breathing patterns (hyperapnea), sleep apnea, abnormal eye and
tongue movements and low muscle tone. Intellect ranges from normal to severe mental
retardation. Joubert syndrome is characterized by a specific finding on an MRI called a molar
tooth sign in which the cerebellar vermis of the brain is absent or underdeveloped and the brain
stem is abnormal.
Joubert syndrome is a very variable condition and the full spectrum of symptoms has not yet
been determined. Several conditions have been described in which the molar tooth sign and
characteristics of Joubert syndrome are present in addition to other findings. It is not yet clear if
these conditions are variants of Joubert syndrome or separate syndromes. These conditions have
been termed Joubert syndrome and related disorders. Some of the other problems that may be
associated with Joubert syndrome include eye abnormalities such as abnormal development of
the retina, abnormality in the iris (coloboma), abnormal eye movements (nystagmus), crossed
eyes (strabismus), and drooping eyelids (ptosis). Other problems sometimes associated with
Joubert syndrome include kidney and/or liver abnormalities, extra fingers and toes (polydactyly),
a gap in the skull with protrusion of the membranes that cover the brain (encephalocele) and
hormone abnormalities.
Causes
Joubert syndrome is inherited as an autosomal recessive genetic disorder.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the
same trait from each parent. If an individual receives one normal gene and one gene for the
disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk
for two carrier parents to both pass the defective gene and, therefore, have an affected child is
25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with

each pregnancy. The chance for a child to receive normal genes from both parents and be
genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have
a higher chance than unrelated parents to both carry the same abnormal gene, which increases the
risk to have children with a recessive genetic disorder.
Ten genes have been identified that cause Joubert syndrome. A mutation in the AHI1 (JBTS3)
gene is responsible for this condition in approximately 11% of families. Affected individuals
with this gene mutation often have impaired vision due to retinal dystrophy. A mutation in the
NPHP1 (JBTS4) gene causes approximately 1-2% of Joubert syndrome. Affected individuals
with this gene mutation often develop a progressive kidney disease called nephronophthisis. A
mutation in the CEP290 (JBTS5) gene causes about 4-10% of Joubert syndrome. Mutations in
the TMEM67 (JBTS6), JBTS1, JBTS2, JBTS7, JBTS8 and JBTS9 genes are also associated with
Joubert syndrome. Other genes responsible for this condition are currently unknown.
Affected Populations
The prevalence of Joubert syndrome has been estimated to be 1/258,000 but is probably an
underestimate of the true prevalence, which may be closer to 1/100,000.
Related Disorders
Several conditions have been described in which the molar tooth sign and characteristics of
Joubert syndrome are present in addition to other findings. It is not yet clear if these conditions
are variants of Joubert syndrome or separate syndromes. The following conditions have been
termed Joubert syndrome and related disorders.
Dekaban-Arima syndrome is characterized by vision abnormalities and kidney dysfunction.
Severe retinal dysplasia is characterized by blindness.
COACH syndrome is characterized by mental retardation, coloboma malformation of the retina
and liver abnormalities.
Senior-Loken syndrome is characterized by vision abnormalities and a type of kidney
dysfunction called nephronophthisis.
Varadi-Papp syndrome is also known as oral-facial-digital syndrome, type VI. This condition is
characterized by cleft lip or palate, tongue abnormalities, extra tissue between the gums, tongue
and mouth, dental abnormalities, facial abnormalities, extra fingers and toes, poor growth and
short stature.
Nephronophthisis is a specific type of kidney dysfunction.
Cogan oculomotor apraxia syndrome is characterized by an eye movement abnormality.

Symptoms of the following disorders can be similar to those of Joubert syndrome. Comparisons
may be useful for a differential diagnosis:
Dandy-Walker malformation is a rare malformation of the brain that is present at birth
(congenital). It is characterized by an abnormally enlarged space at the back of the brain (cystic
4th ventricle) that interferes with the normal flow of cerebrospinal fluid through the openings
between the ventricle and other parts of the brain. Excessive amounts of fluid accumulate around
the brain and cause abnormally high pressure within the skull, swelling of the head (congenital
hydrocephalus), and neurological impairment. Motor delays and learning problems may also
occur. Dandy-Walker malformation is a form of obstructive or internal non-communicating
hydrocephalus, meaning that the normal flow of cerebrospinal fluid is blocked resulting in the
widening of the ventricles. (For more information, choose Dandy Walker as your search term
in the Rare Disease Database.)
Oral-facial-digital syndrome (OFDS) is an umbrella term for at least 10 apparently distinctive
genetic disorders that are characterized by defects and flaws in the development of the structure
of the oral cavity including the mouth, tongue, teeth, and jaw; the development of the facial
structures including the head, eyes, and nose; and the fingers and toes (digits); along with
differing degrees of mental retardation. The presentation of signs and symptoms is extremely
varied, making diagnosis difficult. OFDS type I is the most common of all of these disorders,
and it is quite rare. Each of the other types is extremely rare. (For more information, choose
oral-facial-digital as your search term in the Rare Disease Database.)
Meckel syndrome is a rare inherited disorder characterized by abnormalities affecting several
organ systems of the body (multisystem). Three classic symptoms are normally associated with
Meckel syndrome: protrusion of a portion of the brain and its surrounding membranes
(meninges) through a defect in the back or front of the skull (occipital encephalocele), multiple
cysts on the kidneys (polycystic kidneys), and extra fingers and/or toes (polydactyly). Affected
children may also have abnormalities affecting the head and face (craniofacial area), liver, lungs,
and genitourinary tract. Meckel syndrome is inherited as an autosomal recessive trait. (For more
information, choose Meckel as your search term in the Rare Disease Database.)
Diagnosis
The diagnosis of Joubert syndrome is based on physical symptoms and the "molar tooth sign" as
seen on an MRI. Molecular genetic testing is available for the four genes that have been shown
to cause Joubert syndrome in about 40% of cases. Carrier testing and prenatal diagnosis are
available if one of these gene mutations has been identified in an affected family member.
Standard Therapies
Treatment
The treatment for Joubert syndrome is symptomatic and supportive. Developmental delays are
usually treated with physical therapy, occupational therapy, speech therapy and infant
stimulation. Individuals with Joubert syndrome should be evaluated by appropriate specialists

including nephrologists, ophthalmologists, geneticists and neurologists. Annual screening is

recommended for liver, kidney and retinal abnormalities.
Genetic counseling is recommended for individuals with Joubert syndrome and their families.
Investigational Therapies
Dr. Joseph Gleeson and his team at the University of California, San Diego
Department of Neuroscience, Howard Hughes Medical Institute are interested in identifying new
genes responsible for Joubert syndrome using a combination of approaches. Research is then
carried out to further understand the functional role of these genes during development.
For more information please visit:
http://cbd.ucsd.edu/
Contact: Adrienne Collazo or Kiley Hill
Phone: (858) 822-3786
Fax: (858) 246-0436
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All
studies receiving U.S. Government funding, and some supported by private industry, are posted
on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda,
MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
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