Clinical Utility Gene Card

1. Name of the disease (synonyms)

Hereditary angioedema type III (HAE-III)

Estrogen-related hereditary angioedema

Hereditary angioedema with factor XII mutations (FXII-HAE)

Hereditary angioedema of unknown origin (U-HAE)

2. OMIM# of the disease

610618

3. Name of the analysed genes or DNA/chromosome segments:

Coagulation factor XII; Hageman factor; F12; chromosome 5q.35.2-q35.3

4. OMIM# of the gene(s)

610619

Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in the F12 gene(s) in ⊠ diagnostic, ⊠ predictive and ⊠ prenatal settings and for, ⊠ risk assessment in relatives.

1. Name of the disease (synonyms)

Non-syndromic (isolated and complex) microphthalmia; MCOP.

2. OMIM# of the disease

251600; 610093; 611038; 613094; 611040; 613517; 613704; 615113; 300345; 605738; 610092; 251505; 611638; 613703; 614497; 601186; 615145; 616428; 156900; 156850; 600165; 609549; 611897; 615972.

3. Name of the analysed genes or DNA/chromosome segments

VSX2; RAX; GDF6; MFRP; PRSS56; GDF3; ALDH1A3; SHH; GDF6; ABCB6; STRA6; TENM3; RBP4; MFRP; TMEM98.

4. OMIM# of the gene(s)

142993; 601881; 601147; 606227; 613858; 606522; 600463; 142993; 600725; 601147; 605452; 610745; 610083; 180250; 606227; 615949.

Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in the VSX2, RAX, GDF6, MFRP, PRSS56, GDF3, ALDH1A3, SHH, GDF6, ABCB6, STRA6, TENM3, RBP4, MFRP and TMEM98 genes in ⊠ diagnostic, ⊠ predictive and ⊠ prenatal settings, and for ⊠ risk assessment in relatives.

1. Name of the disease (synonyms)

16p12.1 microdeletion syndrome (hg18/NCBI36). Updated release of the human reference genome (hg19/GRCh37) annotates this region as 16p12.2.

2. OMIM# of the disease

136570.

3. Name of the analysed genes or DNA/chromosome segments

Chromosome 16p12.2 (hg19 chr16:g.(?_ 21950000)_(22470000_?)del).

4. OMIM# of the gene(s)

UQCRC2 (*191329); EEF2K (*606968); CDR2 (*117340); PDZD9 (no OMIM entry); C16orf52 (no OMIM entry); VWA3A (no OMIM entry); and POLR3E (no OMIM entry).

Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in the 16p12.2 region in diagnostic, predictive and prenatal settings, and for risk assessment in relatives.

1. Name of the disease (synonyms)

Deficiency of UDP-galactose:O-beta-d-xylosylprotein 4-d-galactosyltransferase, deficiency of xylosylprotein 4-beta-galactosyltransferase, polypeptide 7, deficiency of galactosyltransferase I, B4GALT7 deficiency, B4GALT7-CDG, progeroid form of Ehlers–Danlos syndrome, type 1, Ehlers–Danlos syndrome with short stature and limb anomalies, Larsen of Reunion Island syndrome.

2. OMIM# of the disease

130070.

3. Name of the analysed genes or DNA/chromosome segments

B4GALT7.

4. OMIM# of the gene(s)

604327.

Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in B4GALT7 in diagnostic, predictive and prenatal settings, and for risk assessment in relatives.

1. Name of the disease (synonyms)

Wolfram syndrome.

2. OMIM# of the disease

222300 and 604928.

3. Name of the analysed genes or DNA/chromosome segments

WFS1 and CISD2.

4. OMIM# of the gene(s)

WFS1 MIM# 606201; CISD2 MIM# 611507.

Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in the WFS1 and CISD2 gene(s) in ⊠ diagnostic, ⊠ predictive and ⊠ prenatal settings and for ⊠ risk assessment in relatives.

1. Name of the disease (synonyms):

There are four subclasses of Congenital Generalized Lipodystrophy (CGL), also named Berardinelli–Seip Congenital Lipodystrophy (BSCL):

Type 1 CGL (CGL1).

Type 2 CGL (CGL2).

Type 3 CGL (CGL3).

Type 4 CGL (CGL4).

2. OMIM# of the disease:

CGL1: #608594.

CGL2: #269700.

CGL3: #612526.

CGL4: #613327.

3. Name of the analysed genes or dna/chromosome segments:

CGL1: AGPAT2.

CGL2: BSCL2.

CGL3: CAV1.

CGL4: PTRF.

4. OMIM# of the gene(s):

AGPAT2: *603100.

BSCL2: *606158.

CAV1: *601047.

PTRF: *603198.

Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in the four gene(s) in ⊠ diagnostic, □ predictive and ⊠ prenatal settings and for ⊠ risk assessment in relatives.

1. Name of the Disease (Synonyms):

Aortic aneurysm, familial thoracic (AAT); aneurysm, thoracic aortic; aortic dissection, familial; thoracic aortic aneurysm and dissection, familial; Alport syndrome, X-linked (ATS); aortic valve disease 1 (AOVD1); bicuspid aortic valve; arterial tortuosity syndrome (ATS); contractural arachnodactyly, congenital, Beals syndrome (CCA); cutis laxa, autosomal dominant 1 (ADCL1); cutis laxa, autosomal recessive, type 1B (ARCL1B); Ehlers–Danlos syndrome, classical type/type I (EDS I); Ehlers–Danlos syndrome, classical type/type II (EDS II); Ehlers–Danlos syndrome, vascular type/type IV (EDS IV); Ehlers–Danlos syndrome, kyphoskoliotic type/type VI (EDS VI); Ehlers–Danlos syndrome, arthrochalasic type/type VIIA (EDS VIIA); familial thoracic aortic aneurysm and aortic dissection; Furlong syndrome (FS); heterotopia, periventricular, Ehlers–Danlos variant (PVNH4); juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JPHT); Loeys–Dietz syndrome type 1 (LDS1/AAT5); Loeys–Dietz syndrome type 2, Marfan syndrome type 2 (LDS2/MFS2/AAT3); Loeys–Dietz syndrome type 3, Aneurysm osteoarthritis syndrome (LDS3/AOS); Loeys–Dietz syndrome type 4 (LDS4); Marfan syndrome (MFS); Moyamoya disease 5 (MYMY5); Shprintzen–Goldberg craniosynostosis syndrome (SGS).

2. OMIM# of the Disease:

109730, 121050, 123700, 130000, 130010, 130010, 130050, 130060, 132900, 154700, 175050, 182212, 208050, 225400, 300537, 301050, 609192, 610168, 611788, 613780, 613795, 614042, 614437, 614816, 615436.

3. Name of the Analysed Genes or DNA/Chromosome Segments:

ACTA2, COL1A1, COL3A1, COL4A5, COL5A1, COL5A2, EFEMP2, ELN, FBN1, FBN2, FLNA, GATA5, MAT2A, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PRKG1, SKI, SLC2A10, SMAD3, SMAD4, TGFB2, TGFB3, TGFBR1, TGFBR2.

4. OMIM# of the Gene(s):

102620, 120150, 120180, 120190, 120215, 130160, 134797, 153454, 160745, 164780, 176894, 190181, 190182, 190198, 190220, 190230, 300017, 303630, 600922, 600993, 601103, 601468, 603109, 604633, 606145, 611496, 612570.

Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing in diagnostic, predictive and prenatal settings and for risk assessment in relatives.

1.Name of the Disease (Synonyms):

Deficiency of UDP-GlcNAc:Dol-P-GlcNAc-P transferase 1, deficiency of Dol-P:GlcNAc-P transferase 1, deficiency of GlcNAc-1-P transferase 1 congenital myasthenic syndrome with tubular aggregates 2, CMSTA2, DPAGT1-CDG, CDG-Ij

2. OMIM# of the Disease:

608093

614750

3. Name of the Analysed Genes or DNA/Chromosome Segments:

DPAGT1

4. OMIM# of the Gene(s):

191350

Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in DPAGT1 gene in diagnostic, predictive and prenatal settings, and for risk assessment in relatives.