18.03.42 Chromosome 19 Flashcards Preview

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Flashcards in 18.03.42 Chromosome 19 Deck (14):

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.

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.