Molecular genetic test information sheets

RAS-MAPK pathway gene sequencing

Genes of the RAS-MAPK pathway are important for growth-factor mediated cell proliferation, differentiation and survival.  Variants in genes of this pathway are responsible for a number of developmental syndromes: Noonan syndrome, LEOPARD syndrome, Costello syndrome and cardio-facio-cutaneous (CFC) syndrome.  This test provides sequencing of >98% for the coding regions and flanking intronic sequences of 13 genes of the RAS-MAPK pathway: BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NF1, NRAS, PTP11, RAF1, SHOC2, SOS1, SPRED1.

For more details please read the RAS-MAPK pathway gene sequencing information sheet (PDF format)


Familial hypertrophic cardiomyopathy (HCM) gene sequencing

HCM can be caused by variants in genes encoding protein components of the cardiac muscle sarcomere. This test provides sequencing of >99% of the coding regions and flanking intronic sequences of 16 cardiac sarcomere genes implicated in development of HCM.  (Variants in some of these genes are also responsible for development of a separate disease, dilated cardiomyopathy.)  Genes tested: ACTC1, CSRP3, FHL1, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, TNNC1, TNNI3, TNNT2, TPM1, TTR.

For more details please read the Familial hypertrophic cardiomyopathy gene sequencing information sheet (PDF format)


Familial dilated cardiomyopathy (DCM) gene sequencing

DCM, like HCM, can also be caused by variants in cardiac sarcomere genes, including several of same genes.  This test provides sequencing of the coding regions and flanking intronic sequences of 13 cardiac sarcomere genes implicated in the development of DCM.  Genes tested: ACTC1, CSRP3, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN, TNNC1, TNNI3, TNNT2, TPM1, TTN.

Titin, a product of the TTN gene, is a giant muscle protein expressed in the cardiac and skeletal muscles.  Because of its size and number of isoforms, TTN has been difficult to sequence and study.  Nevertheless, TTN variants are known to cause congenital myopathies involving cardiac and skeletal muscle, hereditary myopathy with early respiratory failure, tibial muscular dystrophy, and limb-girdle muscular dystrophy and have been shown to segregate with dilated cardiomyopathy (DCM) in a few families.  A 2012 study found variants in the TTN gene, predicted to produce a truncated protein, in approximately ~25% of familial and in ~18% of sporadic cases of DCM.  This test provides sequencing of >99% of the coding regions and flanking intronic sequences of the major cardiac isoform (NM_003319.4) of TTN.

For more details please read the Familial dilated cardiomyopathy gene sequencing information sheet (PDF format)


Alport syndrome gene sequencing

Alport syndrome is the second most common inherited cause of kidney failure.  It is caused by defects in the type IV collagen, an important component of the kidney glomerular basement membrane. Patients commonly experience kidney failure in early adult life and develop deafness at the same time.  Inheritance is X-linked recessive (COL4A5 gene) in 80% of cases. A further 15% have an autosomal recessive form, while in 5% it is inherited as an autosomal dominant (COL4A3 or COL4A4 genes).  This test provides sequencing of >97% of the coding regions and flanking intronic sequences of the COL4A3, COL4A4 and COL4A5 genes.

For more details please read the Alport syndrome gene sequencing information sheet (PDF format)

 

Sequencing of genes associated with neurodegeneration 

Referrals to adult neurology clinics include several diseases such as frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer diesease and Parkinson disease for which the underlying mechanism is neurodegeneration.  Variants in a number of genes have been shown to cause this group of neurological diseases.  This test provides sequencing of >95% of the coding regions and flanking intronic seqences of 15 genes associated with neurodegeneration: APP, CHMP2B, FUS, GRN, LRRK2, MAPT, PARK2, PSEN1, PSEN2, SOD1, SQSTM1, TARDBP, UBQLN2, VAPB, VCP.

For more details please read the Neurodegeneration gene sequencing information sheet (PDF format)

 

Hereditary Haemorrhagic Telangiectasia and Primary Pulmonary Hypertension gene sequencing

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterised by the formation of telangiectasias and arteriovenous malformations (AVMs). Primary pulmonary hypertension (PPH; or primary arterial hypertension, PAH) is a progressive vascular lung disease characterised by increased vascular resistance and arterial pressure, leading to weakening of the heart and eventual heart failure. This test provides sequencing of >97% of the coding and flanking intronic regions of 8 genes associated with HHT and PPH: ACVRL1, BMPR2, CAV1, ENG, GDF2, KCNK3, SMAD4, SMAD9.
 
For more details please read the HHT & PPH gene sequencing information sheet (PDF format)


Ocular malformations gene sequencing
 
Anophthalmia, microphthalmia, coloboma (MAC) and aniridia are severe eye malformations with a total birth incidence of >1 in 5,000. The genetic cause is identifiable in approximately 70% of severe bilateral anophthalmia or severe microphthalmia, 20-30% of bilateral coloboma with or without microphthalmia, and 90% of aniridia.
This test provides sequencing of >99% of coding regions and flanking intronic sequences for 41 genes associated with syndromal and non-syndromal MAC, and aniridia. Genes tested: ACTB, ACTG1, ALDH1A3, BCOR, C12ORF57, CHD7, COL4A1, FOXC1, FOXE3, FZD5, GJA8, ITPA, ITPR1, MAB21L1, MAB21L2, NAA10, OTX2, PAX2, PAX6, PITX2, PITX3, RAB18, RAB3GAP1, RAB3GAP2, RARB, RAX, RBP4, SALL2, SALL4, SHH, SIX3, SMCHD1, SMOC1, SOX2, STRA6, TBC1D20, VAX1, VSX2, YAP1, ZEB2, ZIC2. 
 
For more details please read the Ocular malformation gene panel information sheet (PDF format)


ABCA4 gene sequencing

The ABCA4 gene encodes an adenosine triphosphate (ATP)-binding cassette transporter (ABCR) expressed specifically in the cones and rods of the retina.  Variants in ABCA4 underlie a number of retinal / macular dystrophies: Stargardt disease, an autosomal recessive macular dystrophy often presenting within the first two decades of life, between 30 to 60% of incidences of autosomal recessive cone rod dystrophy and a small proportion of retinitis pigmentosa cases.  This test provides sequencing of >99% of the coding regions and flanking intronic sequences of the ABCA4 gene. 

For more details please read the ABCA4 gene sequencing information sheet (PDF format)


Primordial dwarfism and microcephaly gene sequencing

Primordial dwarfism and microcephaly are genetically diverse disorders of brain and body growth. There are several biological processes that have been implicated in these conditions, such as DNA damage response, DNA replication and centrosome function.  This test provides sequencing of >98 of coding regions and flanking intronic sequences for 50 genes associated with primordial dwarfism and/or microcephaly:  ASPM, ATR, ATRIP, BLM, CASC5, CASK, CDC45, CDC6, CDK5RAP2, CDT1, CENPE, CENPF, CENPJ, CEP135, CEP152, CEP63, CREBBP, DNA2, DPP6, DYRK1A, EP300, GMNN, IGF1, IGF1R, KIF11, LARP7, LIG4, MCPH1, MRE11A, NBN, NDE1, ORC1, ORC4, ORC6, PCNT, PHC1, PLK4, POC1A, RAD50, RBBP8, RNU4ATAC, SRCAP, STIL, TCF4, TRAIP, TUBGCP6, VPS13B, WDR4, WDR62, XRCC4.

For more information please read the  Primordial dwarfism and microcephaly gene sequencing information sheet  (PDF format)

To aid variant interpretation, requests for this test should be accompanied by a completed clinical information form.


Atypical Cornelia de Lange syndrome (CdLS) gene sequencing

Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features, displaying a wide spectrum of severity. Recent evidence shows that there is clinical and molecular overlap between atypical CdLS and other developmental disorders such as KBG syndrome and Wiedemann-Steiner syndrome. Somatic mosaicism has also emerged as a significant disease mechanism in CdLS. This test provides sequencing of >95% of the coding regions and flanking intronic sequences of 7 genes (including somatic mosaic variants): NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11 and KMT2A, and genomic regions containing the known pathogenic variants in AFF4 and NAA10 (p.Arg83Cys). 

For more details please read the Atypical Cornelia de Lange syndrome panel.pdf (PDF format)

Last Reviewed: 18/05/2017