GENETICS

Cystic Fibrosis Screening Questionnaire

This form should be filled out when routine DNA screening for common cystic fibrosis mutations is ordered (480533). The form should be completed by the ordering physician's office and should accompany the sample. Please call 800-345-4363 with any questions.

Patient's name: ________________________________________________

Date of birth: _____________________________ Gender: ____ (M) ____ (F)

Name of person completing form: ________________________________________________________ Physician's signature: ___________________________________________________________________

Indications for Testing

   _____ Routine carrier screening
   _____ Screening for partner of a previously identified carrier
   _____ Routine screening of fetus (either on CVS or amniotic fluid)
   _____ Suspected diagnosis of fetus/symptomatic individual
   _____ Known diagnosis of symptomatic individual

Patient History

Is this patient/this patient's partner currently pregnant? _____ Yes _____ No
If so, what is current gestational age? _____

Has anyone in the patient's family been diagnosed with cystic fibrosis? _____ Yes _____ No
If yes, what is their relationship to the patient (brother, sister, niece, 1st cousin, 2nd cousin, etc)? ___________

Has anyone in the patient's family been identified as a carrier for a cystic fibrosis mutation? _____ Yes _____ No
If yes, what is their relationship to the patient (brother, sister, 1st cousin, 2nd cousin, etc)? ___________
If yes, please list the cystic fibrosis mutation. ___________ Mutation __________ Unknown <

>If this patient is suspected to have cystic fibrosis, what clinical symptoms/ultrasound findings are present? ___________________________
Has the individual been sweat tested? ____ Yes ____ No
Was the sweat test positive? ____ Yes ____ No

Patient Ethnicity
   _____ Ashkenazi Jewish
   _____ Caucasian/White
   _____ African American/Black
   _____ Hispanic
   _____ Asian
   _____ Native American/American Indian
   _____ Other (please specify)__________
   _____ Unknown

Tay-Sachs Disease Screening Questionnaire

This form should be filled out when Tay-Sachs disease biochemical or DNA testing is ordered (tests 510412, 511246, or 510404). The form should be completed by the ordering physician's office and should accompany the sample. Please call 800-345-4363 with any questions.

Tay-Sachs disease is a lysosomal storage disease that causes progressive neurological deterioration. People of Ashkenazi Jewish and French-Canadian ancestry are at increased risk to be carriers of this disorder. There are several methods available for carrier screening, including enzyme testing in serum or leukocytes and direct gene screening for common mutations. Enzyme testing is not mutation-dependent and is suitable for testing in all ethnic groups. Please note that the serum enzyme test is not accurate in pregnant women and women who take oral contraceptives. LabCorp's DNA test identifies 95% of carriers who are Ashkenazi Jewish, but the detection rate is approximately 50% for other ethnic groups. The following information will help us interpret your test results accurately.

Patient's name: _________________________________________________________________________
Date of birth: __________________________________ Gender: _____ M _____ F
Name of person completing form: ________________________________________________________
Physician's signature: ___________________________________________________________________

Patient ethnicity:
   _____ Ashkenazi Jewish
(Eastern European)
   _____ French-Canadian
   _____ Non-Jewish Caucasian
   _____ Sephardic Jewish
(Spanish, Portuguese, or North African)
   _____ Other ________________

Patient history:
Is patient/spouse pregnant? _____ Y _____ N What is the gestational age: _________
Is the patient taking oral contraceptives? _____ Y _____ N
Any other medications in the past 2 weeks? (Please list) ______________________________________________
Has the patient's spouse been identified as a Tay-Sachs carrier? _____ Y _____ N

Indications for testing (check those that apply)
   _____ Routine screening
   _____ Family history of Tay-Sachs. Which family member is affected or a known carrier (eg, brother, niece, uncle)
         ___________________________________________
   _____ Suspected diagnosis. Symptoms: _________________________________________________________
   _____ Sandhoff disease screening
   _____ Other __________________________________________________________________________________

Note: This form should be photocopied as necessary and submitted (with specimens) to the laboratory.

Microdeletion Syndrome Detection

Fluorescence in situ Hybridization (FISH)

Microdeletion syndromes affect every pediatric and genetics practice. The incidence of these syndromes ranges from 1 in 8000 to 1 in 50,000. Diagnosis can be complicated by a negative family history and seemingly normal routine chromosome analysis. LabCorp continues its leadership in the field of diagnostic genetics by making available high resolution chromosome analysis and FISH for many microdeletion syndromes. A partial listing of available tests follows.

Syndrome	Locus	Clinical Features	Probe	% Detectable*	References
Angleman syndrome	15q11.2	Ataxic gait, inappropriate laughter, mental retardation	D15S10	80% (uniparental disomy in <5%)	1,2
Cri-du-chat syndrome	5p15.2	Characteristic cry, microcephaly, mental retardation	D5S23	NA	3
DiGeorge syndrome	22q11.2	Dysmorphic features, hypoplasia/aplasia of thymus and parathyroid	D22S75	>90%	2,4,5
Velocardiofacial syndrome	22q11.2	Cleft palate, cardiac defect, developmental delay	D22S75	85%	5
Kallmann syndrome	Xp22.3	Hypogonadism, ansomia/hyposomia, obesity, mental retardation, short stature, renal abnormalities, cryptorchidism, ataxia/synkinesis	KAL	NA	2,6
Isolated lissencephaly	17p13.3	Lissencephaly	D17S379 / LIS1	≈40%	7
Miller-Dieker syndrome	17p13.3	Mental retardation, dysmorphic features, seizures	D17S379	≥90%	2
Prader-Willi syndrome†	15q11.2	Infant hypotonia, mental retardation, hypogonadism, obesity	SNRPN / DI5S10	70% (uniparental disomy in ≈25%)	2
Smith-Magenis syndrome	17p11.2	Mental retardation, self-destructive behavior, craniofacial changes, sleep disturbances	D17S258	>99%	2,8
Steroid sulfatase deficiency and X-linked ichthyosis	Xp22.3	Absence of STS activity; ichthyosis of extensor and flexor extremities, face, and neck; possible cryptorchidism; corneal opacities, testicular cancer	STS	85%	2
Williams syndrome	7q11.23	Dysmorphic features, cardiac defect, mental retardation, outgoing personality	ELN / LI MK	≥95%	9,10
Wolf-Hirschhorn syndrome	4p16.3	Mental retardation, characteristic facies, psychomotor retardation	D4S96	NA	11
*Deletion detected in those cases that have met strict diagnostic criteria. †FISH performed as a follow-up to a positive RT-PCR test to determine mode of inheritance (test 511139).

References

      1. Buxton J, Chan C, Gilbert H, et al, “Angelman Syndrome Associated With a Maternal 15q11-13 Deletion of Less Than 200 kb,” Hum Mol Genet, 1994, 3(8):1409-13.
      2. Ledbetter D and Ballabio A, “Molecular Cytogenetics of Contiguous Gene Syndromes: Mechanisms and Consequences of Gene Dosage Imbalance,” The Metabolic and Molecular Bases of Inherited Disease, 7th ed, Scriver C, Beaudet A, Sly W, et al, eds, New York, NY: McGraw-Hill, 1995, 811-39.
      3. Overhauser J, Huang X, Gersh M, et al, “Molecular and Phenotypic Mapping of the Short Arm of Chromosome 5: Sublocalization of the Critical Region for the Cri-du-chat Syndrome,” Hum Mol Genet, 1994, 3(2):247-52.
      4. Driscoll D, Budarf M, Emanuel B, et al, “A Genetic Etiology for DiGeorge Syndrome: Consistent Deletions and Microdeletions of 22q11,” Am J Hum Genet, 1992, 50:924-33.
      5. Goldmuntz E and Emanuel B, “Genetic Disorders of Cardiac Morphogenesis,” Circ Res, 1997, 80(4):437-43.
      6. Rugarli E and Ballabio A, “ Kallmann Syndrome,” JAMA, 1993, 270(22):2713-5.
      7. Pilz D, Macha M, Precht K, et al, “Fluorescence in situ Hybridization Analysis With LIS1 Specific Probes Reveals a High Deletion Mutation Rate in Isolated Lissencephaly Sequence,” Genet Med, 1998, 1(1):29-33.
      8. Moncla A, Piras L, Arbex OF, et al, “Physical Mapping of Microdeletions of the Chromosome 17 Short Arm Associated With Smith-Magenis Syndrome,” Hum Genet, 1993, 90(6):657-60.
      9. Ewart A, Morris C, Atkinson D, et al, “Hemizygosity at the Elastin Locus in a Developmental Disorder, Williams Syndrome,” Nat Genet, 1993, 5:11-6.
      10. Osborne L, “Williams-Beuren Syndrome: Unraveling the Mysteries of a Microdeletion Disorder,” Mol Genet Metab, 1999, 67:1-10.
      11. Altherr M, Wright T, Denison K, et al, “Delimiting the Wolf-Hirschhorn Syndrome Critical Region to 750 Kilobase Pairs,” Am J Med Genet, 1997, 71:47-53.