18.03.42 Chromosome 19 Flashcards
What are some features of chromosome 19
F group chromosome Highest gene density Large clustered gene families High GC content High density of repetitive DNA
Give three examples of Mendelian disorders associated with genes on chromosome 19?
1) Myotonic dystrophy type 1 - DMPK - 19q13.32
2) CADASIL - NOTCH 3 - 19p13.2
3) SCA6 - CACNA1A - 19
4) Diamond-Blackdan anaemia - RPS19
Give three examples of cancer related disorders associated with chromosome 19
1) Peutz-Jeghers syndrome/heterdiatry intestinal polyposis synsome - STK11 (TSG) - 19
2) Familial AML with mutation CEBPA - CEBPA -
3) ALL - chromsome rearrangements
4) Oligodendoglimoas - co-deletion of chromosome 1p and 19q
Give three examples of microduplication/deletion syndrome associated with chromosome 19.
1) Microdeletion of 19p13.2
2) Microduplication of 19p13.2
3) 19p13.3 microdeletions
4) 19p13.13 microdup/del syndrome
5) 19q13.11 microdeletion
Give the name of the gene, its position and three clinical features associated with Myotonic dystrophy, type 1.
DMPK 19q13.32 expressed in skeletal muscle.
CTG expansion
myotonia, muscular dystrophy, cataracts, hypogonadism, frontal balding and ECG changes
Give the name of the gene, its position and three clinical features associated with CADASIL.
NOTCH3 - 19p13.12 (AD)
Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1
1) Progressive dementia
2) Mood disorders
3) Migraine
4) Recurrent subcortical cerebral infarctions
Which gene is associated with SCA6, give some clinical features of the disorder.
CACNA1A at 19p13.13. CAG expansion (19+ repeats)
- Cerebellar ataxia
- Dysarthria
- Dysphagia
- Cerebellar atrophy
- Hemiplegic migraine in some patients
- Selective loss of cerebellar Purkinje cells
Gaze-evoked nystagmus - Impaired smooth pursuit
- Abnormal vestibuloocular reflex (VOR)
Which gene is associated with Diamond-Blackfan anaemia give some clinical features of the disorder.
Disorder can be caused by mutations in 70 ribosomal protein genes.
RPS19q13.2 (AD) associated with 25% of cases.
Fatigue Weakness Abnormally pale appearance Webbed neck Short statue Eye problems Increase risk of AML and osteosarcoma
What are some of the features of Peutz-Jeghers syndrome. What gene is this disorder associated with?
Tumour suppressor gene STK11 at 19p13.3
Characterised by the development of benign hamartomatous polyps in GI tract and hyperpigmented macules on lips and oral mucosa. Increased cancer predisposition
Give three clinical features of 19p13.2 microdeletion? What other names is this deletion now recognized by? What is the critical gene?
Typically 0.18Mb-3.4Mb (7-96gene). Candidate gene NFIZ
Also known as Sotos syndrome 2 or Malan syndrome.
1) Macrocephaly
2) Tall stature
3) Delayed delopment of speech and motor skills
4) Moderate ID
5) Seizures
6) Feeding and digestive difficulties
7) Eye abnormalities
What are the features of a microduplication of 19p13.2?
Causes Sotos syndrome-like phenotype. Alters gene expression
1) Variable neuro-cognitive disability
2) Overgrowth
3) Facial dysmorphism similar to Sotos
What are the features of a microdeletion/duplication at 19p13.13
Deletion: developmental delay, overgrowht, macrocephaly with frontal bossing, opthalmalgic and GI findings
Duplication: growth delay and microcephaly.
Smalest region of overalp ~300kb inc 16 genes. Candidates for phenotype include MAST1, NFIX and CALR.
What are the features of a microdeletion at 19q13.11
1) Growth deficiency
2) Microcephaly
3) ID
4) Ectodermal anomalies
5) Genital malformations in males
6) Developmental delay
7) Speech disturbances
Deletion includes 5 genes, inc four zinc-fingers
What phenotype is associated with WIPT1 deletion?
can sometimes be part of larger 19q13.11 deletions. Wilms tumour interacting protein (WIPT1) gene results in hypospadius and is a candidate gene for this genital abnormality, given its WT1 interaction.
Haploinsufficency suggested as underlying mechanism.
