SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03373370

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Project to Accelerate the Diagnosis of TTR Amyloidosis by Use of Molecular Biology in First Intention

Peripheral neuropathies are diseases that affect the nervous system outside the brain and spinal cord, their prevalence is 1% in the general population, the causes are extremely varied with more than 200 identified causes; the main ones are diabetes, excessive alcohol consumption and chemotherapy. They may be sometimes disabling but generally preserve autonomy. Transthyretin amyloidosis is a rare multisystematic hereditary disease with autosomal dominant transmission. They present usually as a peripheral neuropathies (FAP). They are due to a point mutation of the transthyretin gene (chr 18q). FAP is secondary to endoneurial amyloid deposits and are characterized by a slowly progressive sensory, motor and autonomic. FAP is the most severe hereditary polyneuropathy of the adult are irreversible and fatal within 5 to 12 years from onset. Most frequent mutation of TTR gene is located on the second exon; but more than 100 mutations have been reported. Prevalence of FAP is 1 per 1 million inhabitants. They have been reported until 1990s' in four endemic areas North of Portugal, Sweden, Japan and Majorca. In these areas, diagnosis is facilitated because of the stereotypical presentation : a length-dependent polyneuropathy with predominant involvement of thermal and pain sensations and autonomic dysfunction, early onset in the third decade and a predominant Met30 TTR mutation. Positive family history is frequent 85% (one of the parents is affected). Diagnosis requires detection of TTR mutation by molecular biology (blood sample) and characterization of amyloid deposit on labial salivary gland biopsy.

NCT03373370 Polyneuropathy Diagnosis Idiopathic Progressive Neuropathy
MeSH: Amyloidosis Polyneuropathies
HPO: Amyloidosis Motor polyneuropathy Polyneuropathy


Primary Outcomes

Description: Rate of amyloidogenic TTR mutation in progressive idiopathic polyneuropathy

Measure: Rate of amyloidogenic TTR mutation

Time: 1 day

Secondary Outcomes

Description: Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : disabling neuropathy (including ataxic).

Measure: To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy

Time: 1 day

Description: Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy :variant Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Measure: To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy :variant Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Time: 1 day

Description: Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : upper limb onset neuropathy.

Measure: To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : upper limb onset neuropathy.

Time: 1 day

Time Perspective: Prospective

Cohort


There is one SNP

SNPs


1 V30M

Conversely to endemic areas, look for V30M mutation is not enough to exclude TTR-FAP, TTR gene sequencing is required. --- V30M ---



HPO Nodes


HPO:
Amyloidosis
Genes 22
SLC7A7 PSEN2 FGA ITM2B LYZ TTR NLRP1 POLA1 APOA1 SAA1 MEFV PRNP NLRP3 IL31RA GSN B2M RET APOE OSMR TNFRSF1A APP CST3
Motor polyneuropathy
Genes 25
SLC5A7 SLC12A6 ALDH18A1 SCO2 TRPV4 GJC2 CHAT SPG11 BSCL2 HINT1 SELENOI SYT2 SNAP25 COL13A1 REEP1 ARL6IP1 TFG MYO9A AGRN SLC18A3 SLC25A1 GARS PPOX VAMP1 CTDP1
Polyneuropathy
Genes 52
SLC12A6 MYD88 ERCC8 SH3TC2 DMXL2 LDB3 RPIA SETX ERCC6 MYOT ATP7B ATP6 PSAP DHH COX3 ARL6IP1 CYTB GCLC AIFM1 PDK3 SEPTIN9 DGUOK PDYN C12ORF65 ND1 ND2 ND4 ND4L ND5 FAM126A ND6 CD59 PEX12 CYP7B1 ALAD FUCA1 ABCD1 NGLY1 PEX11B GRM1 SLC25A19 ABHD12 TTR PIK3R5 NAGS COQ7 EDNRB GSN TBC1D24 PMM2 SNAP29 PRPS1