Common constitutional diseases per chromosome

Question 1

Common constitutional and acquired diseases for Chromosome 1

Answer 1

• 1p36 deleion. 1 in 5,000 newborns.0.5% of idiopathic intellectual disability. Most common terminal subtelomeric microdeletion syndrome. ID, hypotonia, growth retardation, hearing loss, seizures, cataracts. ALso a duplication of this: milder phenotype, ID, hypotonia, cataracts
• Small supernumary ring chromosome 1. Mostly de novo but can be inherited (maternal transmission more common). Correlation between karyotype and phenotype difficult due to size of ring, euchromatic content, proportion of mosaicism. Dev delay, hypotonia, slow growth.
• MTHFR gene. AR. Homocystinuria due to MTHFR deficiency, a common inborn error of folate metabolism. increased excretion of homocysteine in the urine, ID, seizures,
• Maple syrup urine disease (MSUD) AR. Metabolic crisis- hypertonia, spasticity, lethargy. DBT gene is on chr 1 (1 of 4 proteins that form the branched-chain alpha-keto acid dehydrogenase complex (BCKD)).
• MCADD (Medium-chain acyl-CoA dehydrogenase deficiency). 1:4000 to 1:17,000. AR mutations in ACADM. 985A>G common mutation

Question 2

Common constitutional and acquired diseases for Chromosome 2

Answer 2

• MSH2 & MSH6.
• TTN
• RNU4ATAC
• 2p15-16.1 microdeletion syndrome

Question 3

Common constitutional and acquired diseases for Chromosome 3

Answer 3

• MLH1
• VHL
• PIK3CA
• 3q29 microdeletion syndrome

Question 4

Common constitutional and acquired diseases for Chromosome 4

Answer 4

• HTT. Huntington Disease.
• FGFR3- achodroplasia.

Question 5

Common constitutional and acquired diseases for Chromosome 5

Answer 5

• 5p-, deletion of the long arm of chromosome 5. Cri du chat syndrome
• SMN1/2, SMA.
• APC. Familial adenomatous polyposis

Question 6

Common constitutional and acquired diseases for Chromosome 6

Answer 6

• PARK2
• BCKDHB:maple syrup urine disease

Question 7

Common constitutional and acquired diseases for Chromosome 7

Answer 7

• CFTR. Cystic Fibrosis.
• Williams syndrome= deletion of 7q11.23

Question 8

Common constitutional and acquired diseases for Chromosome 8

Answer 8

• CHD7= CHARGE syndrome
• MCPH1= primary microcephaly
• 8p23.1 duplication syndrome
• t(8;14)(q24;q32)- Burkitt lymphoma. MYC-IGH

Question 9

Common constitutional and acquired diseases for Chromosome 9

Answer 9

• chronic myeloid leukemia (CML)= t(9;22)(q34;q11) BCR-ABL1
• FXN. Friedreich ataxia
• TSC1: tuberous sclerosis complex 1
• TGFBR1: Loeys-Dietz syndrome 1

Question 10

Common constitutional and acquired diseases for Chromosome 10

Answer 10

• RET: Multiple endocrine neoplasia type 2- GOF mutations. Proto-oncogene.. LOF= hirschsprung disease
• PTEN. Tumour suppressor gene, negatively regulating the Akt/PKB signaling pathway

Question 11

Common constitutional and acquired diseases for Chromosome 11

Answer 11

• ATM= ataxia telangiectasia
• HBB= beta thalassemia
• MEN1= Multiple endocrine neoplasia type 1
• WT= Wilms tumour
• Beckwith-Weidemann syndrome= 11p15.5. Paternal UPD, deletion of maternal allele, imprinting. Overgrowth, hemihypetrophy, renal abnormalities.
• Ewing sarcoma. t(11;22)(q24;q12) EWSR1-FLI1.

Question 12

Common constitutional and acquired diseases for Chromosome 12

Answer 12

-

Question 13

Common constitutional and acquired diseases for Chromosome 13

Answer 13

-Trisomy 13, Patau’s syndrome

Question 14

Common constitutional and acquired diseases for Chromosome 14

Answer 14

-

Question 15

Common constitutional and acquired diseases for Chromosome 15

Answer 15

-Deletion of part of short arm of chromosome 15, paternal copy, Prader Willi syndrome

Question 16

Common constitutional and acquired diseases for Chromosome 16

Answer 16

-

Question 17

Common constitutional and acquired diseases for Chromosome 17

Answer 17

-

Question 18

Common constitutional and acquired diseases for Chromosome 18

Answer 18

-Trisomy 18, Edward’s syndrome

Question 19

Common constitutional and acquired diseases for Chromosome 19

Answer 19

5

Question 20

Common constitutional and acquired diseases for Chromosome 20

Answer 20

/

Question 21

Common constitutional and acquired diseases for Chromosome 21

Answer 21

-

Question 22

Common constitutional and acquired diseases for Chromosome 22

Answer 22

8

Question 23

Common constitutional and acquired diseases for Chromosome X

Answer 23

-Fragile X, FXTAS, POI. FMR1 expansion. -Trisomy (47,XXY) Klinefelter’s Syndrome, Monosomy (45,X) Turner syndrome -SBMA. Androgen receptor gene expansion. -DMD. Duchenne/ becker md

Question 24

Common constitutional and acquired diseases for Chromosome Y

Answer 24

-Y chromosome microdeletions and infertility. - XYY -XXY (Klinefelter syndrome)