Chromosome Locations Flashcards
1
Q
Wolf Hirschhorn
A
4p16.3
2
Q
Cri-du-chat
A
5p15.3
3
Q
Williams
A
7q11.23 (submicroscopic), can be missed by karyotype, need CMA
4
Q
WAGR
A
Wilms, aniridia, GU, DD
11p13
5
Q
Beckwith Wiedemann
A
11p15.5
KCNQOTI and H19
6
Q
Prader Willi/Angelman
A
15q11.2-q13.1
7
Q
Smith Magenis
A
17p11.2
8
Q
Miller Dieker
A
17p13.3
9
Q
NF1
A
17q11.2
Neurofibromin
Women increased risk of breast cancer and should have enhanced screening between 30-50 years
10
Q
Sotos
A
5q35
NSD1
MLPA or FISH
macrocephaly, pointed chin, tall, obesity, DD, advanced bone age
sometimes seizures, psych, AOM, constipation, risk of tumors (~1%, no screen recommended)
11
Q
Transient Neonatal DM
A
Paternal UPD 6
Imprinting 6q24
HYMAI, PLAGL1
12
Q
Silver Russell
A
Maternal UPD 7
Imprinting 11p
Structural chromosome aberration
Hypomethylation of the paternal IC1 site on chromosome 11 explains about 45% of cases of Russell-Silver syndrome
macrocephaly, hypospadias, delayed bone age
13
Q
BWS
A
Imprinting 11p
Paternal UPD 11p
Gene change, ex CDKN1C
Paternal duplication, inv, translocation
Gain of methylation or microdeletion of the maternal IC1 site of chromosome 11
14
Q
Maternal UPD 14
A
SS, hypotonia, precocious puberty, truncal obesity, variable psychomotor retardation
15
Q
Paternal UPD 14
A
Severe psychomotor retardation, polyhydramnios, finger contractures, bell shaped thorax with coat hanger sign ribs
16
Q
PWS
A
Microdeletion (70%)
Maternal UPD 15 (25%)
Imprinting
17
Q
Angelman
A
Microdeletion (70%)
Paternal UPD 15 (1-3%)
UBE3A mutation (5-10%)
Imprinting (3-5%)
18
Q
Juvenile Polyposis Coli
A
BMPR1A
SMAD4 - also HHT
19
Q
Peutz Jeghers
A
STK11
50% del
45% truncating
Risk of intussusception at any age!
Lifetime cancer risk 81%, mostly GI, CRC, esophageal, pancreatic
32% breast cancer risk
20
Q
GREM1 Polyposis
A
5’ 40kb duplication
Mixed Polyposis with adentomatous, juvenile, and hyperplastic
21
Q
Lynch
A
Also known as hereditary non Polyposis colon cancer (HNPCC)
CRC, endometrial, bile duct, ovarian, ureteral, and gliomas
PMS2, EPCAM, MSH2 and MLH1
22
Q
Breast-Ovarian
A
BRCA1/2
BRCA2 < BRCA1 for ovarian
23
Q
Cowden
A
PTEN syndromic features
Thyroid
Breast
24
Q
Hereditary Breast Cancer
A
PALB2
CHEK2
ATM heterozygotes (colon, pancreatic, breast)
25
Breast+Gastric
CDH1
With or without cleft palate
26
Ovarian
RAD51C
27
BRCA2
Male breast cancer
Pancreatic
Prostate
Melanoma
28
Bloom
AR, BLM
SS, photosensitive skin, immunodeficiency
Leukemia, lymphoma, solid tumors
29
Werner
AR, WRN
Premature aging, cataracts, diabetes, atherosclerosis
Soft tissue sarcomas and skin cancers
DNA helicase defect (stop codon causing nonsense or frameshift)
30
NF2
Chromosome 22 for merlin
31
Schwannomatosis
Chromosome 22
SMARCB1 or LZTR1
32
Parkinson Disease
GBA1 - late onset
SNCA - alpha synuclein, AD
LRRK2 - onset >50, incomplete penetrance, AD
PRKN - early onset, AR
DNAJC6 - juvenile onset, DD, seizures, AR
TAF1 - XLR
33
DYT5
Dystonia, AD
DOPA responsive
Also DNAJC12 and SLC18A2
34
Huntington Repeats
General Population <26 repeats
Intermediate 27-35
HD = 36+
Reduced penetrance 36-39 repeats
CAG
Paternal inheritance in some cases is associated with the juvenile presentation of Huntington disease, with rigidity
35
Fragile X
CGG
200+ repeats
55-200 = can expand
80% have ADHD
36
GAA
Friedreich Ataxia
GAA expansions usually 90+, but in 300+ range
If one expansion and one normal, either a carrier or has the disease. To differentiate this, must point mutation analysis to confirm disease present.
37
CAG
HD
SCA
DRP atrophy
Spinal and bulbar atrophy
38
CTG
Myotonic dystrophy
39
Hereditary Spastic Paraplegia
AD: SPAST, ATLI, KIF5A, REEP1
AR: SPG11
XLR: L1CAM, PLP1
40
Myotonic Dystrophy
CTG repeat expansion in DMPK gene
41
Facioscapulohumeral Dystrophy
Weakness in facial and girdle muscles, retinal vasculopathy, sensorineural hearing loss, extreme lordosis
DUX4 gene on 4q
D4Z4 reduced number of repeats causes issues
>12 repeats normal
10-11 reduced penetrance
<9 full penetrance
42
PCR Steps
Denaturation
Annealing primer to ssDNA
Extension/synthesis
Copies after n cycles
43
Menkes vs Wilsons
ATP7A - Menkes
ATP7B - Wilson
44
Hereditary hemochromatosis
C282Y and H63D in HFE
Prussian blue staining, Kupffer cells in hepatocytes
45
ADHD
VNTR
46
Asperger
GABRB3
47
Multiple pterygium syndrome
Acetylcholine receptor mutation on 2p37
48
Trimethylaminuria
Dimethylglycine dehydrogenase deficiency
49
Repeat Expansion Disorders: Locations of mutations within the gene
Fragile X - expansion in promotor region of 5’ UTR
Friedreich ataxia - intron
Huntington and spinocerebellar - exons
Myotonic dystrophy - 3’ UTR
50
Torsion Dystonia
GAG deletion in DYT1 gene
51
Simpson Golabi Behmel
Coarse facies
Postaxial polydactyly
Macrosomia
Cardiac conduction defects
52
Mutations in Cancer Risk: Down Syndrome, Proteus Syndrome, ETV6, IKZF1, and RUNX1
Somatic GATA1 mutations are seem in almost all cases of TMP which is a frequent complication of children with Down syndrome.
AKT undergoes somatic mutation in Proteus syndrome
ETV6 is a translocation partner in AML
IKZF1 mutations and deletions are common in ALL
RUNX1 deletions and mutations cause familial platelet disorder with AML
53
Dyskeratosis Congentia
leukoplakia, abnormal nails and evidence of bone marrow failure
DKC have telomeres that are shorter than 1% for age
54
Definitions: pleiotrophy, locus heterogeneity, and allelic heterogeneity
Locus heterogeneity refers to the production of identical phenotypes by mutations at two or more different loci. Ex. Disease that has multiple causative genes, such as OI, RP, Noonan, etc.
Pleiotropy refers to disorders in which a single gene or gene pair causes multiple phenotypes, especially when the effects are not obviously related. Ex. Marfan, Holt Oram, etc.
Allelic heterogeneity refers to the situation when different alleles of a single gene produce the same/similar phenotypes. Ex. Beta thal, CF, PKU.
55
Tay Sachs Detection in Prenatal Counseling: husband has affected sister and wife is not Jewish and no TS family hx
the BEST answer might be serum HexA on husband (+/- molecular) and WBC hexA on the wife. The major points of this question are (1) serum hexA is not accurate during pregnancy and one needs to do WBC hexA determinations and (2) molecular testing is not helpful in the non-Ashkenazi Jewish population since most mutations will not be detected.
56
SCID Genes
ZAP70 causes AR SCID
IL2RG mutations are found in > 99% of males with SCID
57
HOXA13
Hand-foot-uterus syndrome is due to mutations in HOXA13
58
Saathre Chotzen
TWIST1
Most people with Saethre-Chotzen syndrome have prematurely fused skull bones along the coronal suture, the growth line that goes over the head from ear to ear.
59
Witkop Syndrome
MSX1
Ectodermal dysplasia - thin, friable nails
Normal hair, able to sweat
60
Gorlin Syndrome Cancers
Basal cell skin cancer
Medulloblastoma
61
CPTI vs CPTII
CPTI - presents with liver disease
CPTII - rhabdo with strenuous exercise, high CK, renal (+myoglobinuria), usually presents later in life
62
MENI, MENIIA, MENIIB
MENI - parathyroid, pancreatic, pituitary
MENIIA - thyroidectomy is recommended to be performed by age 5; parathyroid, medullary thyroid, and pheochromocytoma
MENIIB - prophylactic thyroidectomy is recommended by age 1; marfan habitus, pheochromocytoma, medullary thyroid
63
Stickler Syndrome
AD
retinal detachment
Robin sequence in infants
Arthropathy, juvenile rheumatoid arthritis
64
Ectodermal Dysplasia
Also known as hidrotic ectodermal dysplasia
EDAR = AR or AD
EDA1 = X linked
palmo-plantar hyperkeratosis, normal sweating and teeth
65
Charcot Marie Tooth vs. Hereditary neuropathy with liability to pressure palsies (HNPP)
CMT: PMP22, 17p12 duplication
Hereditary neuropathy with liability to pressure palsies (HNPP): 17p12 deletion
66
PTCH1
Gorlin sydrome
67
SMARCB1
Results in rhabdoid tumor
68
SUFU
medulloblastoma
69
DICER1
pleuropulmonary blastoma, multinodular goiter (benign), and rhabdosarcoma
70
The most common pathogenic variants that result in the disorder gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) represent which of the following mutational mechanisms?
Promotor region
GAPPS is a disorder with a specific genotype/phenotype relationship. It results from noncoding promoter variants that alter the YY1 transcription factor binding site in the APC promoter 1B. This disorder is distinct from familial adenomatous polyposis which can result from nonsense and other loss of function variants in APC.
71
Fraser syndrome
Syndactyly, crytophthalmos, external ear abnormalities, midline nasal cleft, widely-spaced nipples, and cryptorchidism
72
Fumarate hydratase cancer associations
hereditary leiomyomatosis with renal cell cancer (HLRCC) which is caused by heterozygous mutations (AD)
73
CVID
TNFRSF13B (TACI)
74
Spondyloepiphyseal dysplasia congenita
malar hypoplasia, cleft palate, decreased mobility of elbows, knees and hips and club feet but not macrocephaly or brachydactyly
75
Pseudochondroplasia
short stature, normal facial appearance and brachydactyly but later onset than Hypochondroplasia
Cartilage oligomeric matrix protein
76
Hypochondroplasia
Hypochondroplasia has short stature, macrocephaly, normal facial appearance and palate, short limbs and brachydactyly but no trident hand
77
Multiple Epiphyseal Dysplasia
chronic hip and knee pain and decreased ROM of his hips and knees
May require early age hip and knee replacements
78
AR disorders with significant malignancy risk
Some autosomal recessive disorders with substantial risk of malignancy are glycogen storage disease type I, tyrosinemia, hemochromatosis, and others less prominently. Immunodeficiency disorders and DNA repair disorders also relevant.
79
Hypermutated colon cancer
POLE
80
Dystrophic epidermolysis bullosum
Scarring in the dermis can be AD or AR and is associated with COL7A1 mutations (below basement membrane)
81
Junctional Epidermolysis bullosum
AMB3 is associated with junctional EB, where severe scarring is in the basement membrane
82
Simplex Epidermolysis bullosum
scarring in the basal layer (epidermis)
EXPH5
KRT14
TGM5
83
Jervell and Lange-Nielsen
Jervell and Lange-Nielsen syndrome is associated with congenital deafness and long QT interval
KCNQ1/E1
84
Meckel Syndrome
microcephaly, an occipital meningoencephalocele, renal cysts/polycystic kidneys and post-axial polydactyly
85
Non-allelic homologous recombination (NAHR) Resulting disorders
22q11.2 del
Sotos
86
Cardiomyopathy Dilated vs Hypertrophic
Hypertrophic: MYH7
Dilated: TTN
87
Defective protein responsible for familial hypercholesterolemia
LDL receptor
88
Joubert Syndrome
congenital ataxia, hypotonia, episodic breathing and intellectual disability
Renal dystrophy
89
GALNT3-CDG
tumoral calcinosis with vascular calcification, painful ectopic periarticular calcification, increased renal tubular reabsorption of phosphate, retinal angioid streaks
90
MPI-CDG
cyclic vomiting, profound hypoglycemia, failure to thrive, liver fibrosis, and protein-losing enteropathy, and occasionally coagulopathy
91
PGM1-CDG
dilated cardiomyopathy, chronic hepatitis, fatigue, and Pierre Robin sequence with cleft palate
92
PMM2-CDG
microcephaly, prominent forehead, nystagmus, large ears, flat nasal bridge, thin upper lip as well as hypotonia, intellectual disability, seizures, cerebellar hypoplasia, liver disease, pericardial effusions and lipodystrophy
93
Pallister Hall
hypothalamic hamartoblastoma, hypopitutarism, imperforate anus, and postaxial polydactyly
94
Neu-Laxova
microcephaly or lisssencephaly, elfin-facies with exophthalmos, and syndactyly with subcutaneous edema
95
Warburg Syndrome
agyria, cerebellar hypoplasia, Dandy-Walker cyst, microphthalmia, and retinal detachment with retinal dysplasia
96
Ellis-van Creveld syndrome
rhizomelia, short and narrow chest, polydactyly, hypoplastic nails, fine hair, conical teeth, hypodontia
97
OI Types I - IV
Type I. Mildest and most common type.
Type II. Most severe type.
Type III. Most severe type in babies who don't die as newborns.
Type IV. Symptoms are between mild and severe
98
Costello
HRAS
HCOM
neuroblastoma
rhabdomyosarcoma
99
Fanconi Anemia
chromosome breakage syndrome -> triradial and quadriradial chromosomes
SS, hypogonadism, DD, abnormal pigmentation, progressive bone marrow failure, aplastic anemia, myelodysplastic syndrome, AML, ear, heart, CNS malformation, preaxial polydactyly
Avoid sun exposure
100
Congenital Contractural Arachnodactyly
Beals syndrome, FBN2
severe contractures, crumpled ears, marfanoid, kyphosis/scoliosis, aortic dilation, malrotation, heart defects
101
EDS Kyphoscoliotic Type
PLOD1
102
Lowes Dietz
TGFBR1/2, SMAD3
Similar symptoms to vascular EDS, but with skeletal findings of Marfan (pectus)
Bifid uvula, cleft palate, hypertelorism
